JPWO2018079740A1 - 癌の治療及び/又は予防用医薬組成物 - Google Patents
癌の治療及び/又は予防用医薬組成物 Download PDFInfo
- Publication number
- JPWO2018079740A1 JPWO2018079740A1 JP2017563359A JP2017563359A JPWO2018079740A1 JP WO2018079740 A1 JPWO2018079740 A1 JP WO2018079740A1 JP 2017563359 A JP2017563359 A JP 2017563359A JP 2017563359 A JP2017563359 A JP 2017563359A JP WO2018079740 A1 JPWO2018079740 A1 JP WO2018079740A1
- Authority
- JP
- Japan
- Prior art keywords
- seq
- amino acid
- acid sequence
- chain variable
- variable region
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 172
- 201000011510 cancer Diseases 0.000 title claims abstract description 93
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title abstract description 17
- 230000002265 prevention Effects 0.000 title abstract description 13
- 239000012634 fragment Substances 0.000 claims abstract description 204
- 239000012190 activator Substances 0.000 claims abstract description 75
- 230000009257 reactivity Effects 0.000 claims abstract description 71
- 230000001900 immune effect Effects 0.000 claims abstract description 53
- 101710072528 Caprin-1 Proteins 0.000 claims abstract description 16
- 102100029949 Caprin-1 Human genes 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 150000001413 amino acids Chemical class 0.000 claims description 829
- 108090000623 proteins and genes Proteins 0.000 claims description 115
- 102000004169 proteins and genes Human genes 0.000 claims description 108
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 87
- 238000000034 method Methods 0.000 claims description 55
- -1 imidazoquinoline compound Chemical class 0.000 claims description 46
- 239000000556 agonist Substances 0.000 claims description 41
- 239000003446 ligand Substances 0.000 claims description 41
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 29
- 229920001184 polypeptide Polymers 0.000 claims description 26
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 26
- 210000000170 cell membrane Anatomy 0.000 claims description 23
- 102000002689 Toll-like receptor Human genes 0.000 claims description 22
- 108020000411 Toll-like receptor Proteins 0.000 claims description 22
- 206010006187 Breast cancer Diseases 0.000 claims description 17
- 208000026310 Breast neoplasm Diseases 0.000 claims description 17
- 102000003930 C-Type Lectins Human genes 0.000 claims description 10
- 108090000342 C-Type Lectins Proteins 0.000 claims description 10
- 102000012064 NLR Proteins Human genes 0.000 claims description 10
- 108091005686 NOD-like receptors Proteins 0.000 claims description 10
- 206010025323 Lymphomas Diseases 0.000 claims description 9
- 239000002158 endotoxin Substances 0.000 claims description 9
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 108020004414 DNA Proteins 0.000 claims description 7
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 claims description 7
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 claims description 7
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims description 7
- 102100033110 Toll-like receptor 8 Human genes 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 claims description 6
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 claims description 6
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 claims description 6
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 claims description 6
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
- 206010038389 Renal cancer Diseases 0.000 claims description 6
- 206010039491 Sarcoma Diseases 0.000 claims description 6
- 102100024333 Toll-like receptor 2 Human genes 0.000 claims description 6
- 102100024324 Toll-like receptor 3 Human genes 0.000 claims description 6
- 102100039360 Toll-like receptor 4 Human genes 0.000 claims description 6
- 102100039357 Toll-like receptor 5 Human genes 0.000 claims description 6
- 201000010982 kidney cancer Diseases 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 201000002528 pancreatic cancer Diseases 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 206010005003 Bladder cancer Diseases 0.000 claims description 5
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 5
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 5
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 201000004101 esophageal cancer Diseases 0.000 claims description 5
- 201000010175 gallbladder cancer Diseases 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 201000010536 head and neck cancer Diseases 0.000 claims description 5
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 201000007270 liver cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 102000005962 receptors Human genes 0.000 claims description 5
- 108020003175 receptors Proteins 0.000 claims description 5
- 201000011549 stomach cancer Diseases 0.000 claims description 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 206010046766 uterine cancer Diseases 0.000 claims description 5
- 208000017604 Hodgkin disease Diseases 0.000 claims description 4
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 4
- 101000763537 Homo sapiens Toll-like receptor 10 Proteins 0.000 claims description 4
- 101001057748 Human cytomegalovirus (strain AD169) Uncharacterized protein IRL7 Proteins 0.000 claims description 4
- 206010027406 Mesothelioma Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 4
- 206010057644 Testis cancer Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 claims description 4
- 102100027009 Toll-like receptor 10 Human genes 0.000 claims description 4
- 102100033117 Toll-like receptor 9 Human genes 0.000 claims description 4
- 229920000392 Zymosan Polymers 0.000 claims description 4
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 claims description 4
- 201000003120 testicular cancer Diseases 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 claims description 3
- 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 claims description 3
- 108020000946 Bacterial DNA Proteins 0.000 claims description 3
- 108010058432 Chaperonin 60 Proteins 0.000 claims description 3
- 108010040721 Flagellin Proteins 0.000 claims description 3
- 102000004895 Lipoproteins Human genes 0.000 claims description 3
- 108090001030 Lipoproteins Proteins 0.000 claims description 3
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 claims description 3
- 108010013639 Peptidoglycan Proteins 0.000 claims description 3
- 102000011195 Profilin Human genes 0.000 claims description 3
- 108050001408 Profilin Proteins 0.000 claims description 3
- 101001057744 Human cytomegalovirus (strain AD169) Uncharacterized protein IRL9 Proteins 0.000 claims description 2
- 101710120431 Protein IRL10 Proteins 0.000 claims description 2
- 229940124669 imidazoquinoline Drugs 0.000 claims description 2
- VQWNELVFHZRFIB-UHFFFAOYSA-N odn 1826 Chemical compound O=C1NC(=O)C(C)=CN1C(O1)CC(O)C1COP(O)(=O)OC1CC(N2C(NC(=O)C(C)=C2)=O)OC1COP(O)(=O)OC1CC(N2C3=C(C(NC(N)=N3)=O)N=C2)OC1COP(O)(=O)OC1CC(N2C(N=C(N)C=C2)=O)OC1COP(O)(=O)OC1CC(N2C3=NC=NC(N)=C3N=C2)OC1COP(O)(=O)OC1CC(N2C3=C(C(NC(N)=N3)=O)N=C2)OC1COP(O)(=O)OC1CC(N2C(NC(=O)C(C)=C2)=O)OC1COP(O)(=O)OC1CC(N2C(N=C(N)C=C2)=O)OC1COP(O)(=O)OC1CC(N2C(N=C(N)C=C2)=O)OC1COP(O)(=O)OC1CC(N2C(NC(=O)C(C)=C2)=O)OC1COP(O)(=O)OC(C(O1)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(O)=O)CC1N1C=C(C)C(=O)NC1=O VQWNELVFHZRFIB-UHFFFAOYSA-N 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 77
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims 2
- 210000003630 histaminocyte Anatomy 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 48
- 230000003308 immunostimulating effect Effects 0.000 abstract description 9
- 239000000562 conjugate Substances 0.000 description 388
- 241000699666 Mus <mouse, genus> Species 0.000 description 177
- 235000018102 proteins Nutrition 0.000 description 104
- 210000004027 cell Anatomy 0.000 description 78
- 239000000243 solution Substances 0.000 description 60
- 241000699670 Mus sp. Species 0.000 description 42
- 239000002253 acid Substances 0.000 description 32
- 229920001223 polyethylene glycol Polymers 0.000 description 31
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 28
- 229960000575 trastuzumab Drugs 0.000 description 28
- 229950010550 resiquimod Drugs 0.000 description 26
- 239000013642 negative control Substances 0.000 description 25
- 150000002148 esters Chemical class 0.000 description 20
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 16
- 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 14
- 125000003396 thiol group Chemical group [H]S* 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000012228 culture supernatant Substances 0.000 description 12
- 125000003277 amino group Chemical group 0.000 description 11
- 229940125644 antibody drug Drugs 0.000 description 11
- 102000036639 antigens Human genes 0.000 description 11
- 108091007433 antigens Proteins 0.000 description 11
- 238000007796 conventional method Methods 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 11
- 150000003573 thiols Chemical class 0.000 description 11
- 239000000427 antigen Substances 0.000 description 10
- 239000008363 phosphate buffer Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 239000011616 biotin Substances 0.000 description 9
- 229960002685 biotin Drugs 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 235000020958 biotin Nutrition 0.000 description 7
- 230000021615 conjugation Effects 0.000 description 7
- 238000010561 standard procedure Methods 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 230000001268 conjugating effect Effects 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 5
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 101710120037 Toxin CcdB Proteins 0.000 description 4
- HYSPJPGXSALJRR-DHIFEGFHSA-N [4-[[(2s)-5-(carbamoylamino)-2-[[(2s)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=O)C(=O)NC=1C=CC(COC(=O)OC=2C=CC(=CC=2)[N+]([O-])=O)=CC=1)C(=O)CCCCCN1C(=O)C=CC1=O HYSPJPGXSALJRR-DHIFEGFHSA-N 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
- 229960005395 cetuximab Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000012948 isocyanate Substances 0.000 description 4
- 150000002513 isocyanates Chemical class 0.000 description 4
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 210000000214 mouth Anatomy 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000001235 sensitizing effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- FLCQLSRLQIPNLM-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-acetylsulfanylacetate Chemical compound CC(=O)SCC(=O)ON1C(=O)CCC1=O FLCQLSRLQIPNLM-UHFFFAOYSA-N 0.000 description 3
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 3
- SSZHESNDOMBSRV-UHFFFAOYSA-N 6-amino-2-(butylamino)-9-[[6-[2-(dimethylamino)ethoxy]pyridin-3-yl]methyl]-7h-purin-8-one Chemical compound C12=NC(NCCCC)=NC(N)=C2NC(=O)N1CC1=CC=C(OCCN(C)C)N=C1 SSZHESNDOMBSRV-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 3
- 229930182474 N-glycoside Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 3
- 239000000611 antibody drug conjugate Substances 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 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 3
- 229920005686 brominated PEG Polymers 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 238000011033 desalting Methods 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 229940127121 immunoconjugate Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 201000006512 mast cell neoplasm Diseases 0.000 description 3
- YZOQZEXYFLXNKA-UHFFFAOYSA-N n-[4-(4-amino-2-ethylimidazo[4,5-c]quinolin-1-yl)butyl]methanesulfonamide Chemical compound C1=CC=CC2=C(N(C(CC)=N3)CCCCNS(C)(=O)=O)C3=C(N)N=C21 YZOQZEXYFLXNKA-UHFFFAOYSA-N 0.000 description 3
- 229950006780 n-acetylglucosamine Drugs 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- FXYPGCIGRDZWNR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)CCC1=O FXYPGCIGRDZWNR-UHFFFAOYSA-N 0.000 description 2
- DIYPCWKHSODVAP-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 DIYPCWKHSODVAP-UHFFFAOYSA-N 0.000 description 2
- FHJATBIERQTCTN-UHFFFAOYSA-N 1-[4-amino-2-(ethylaminomethyl)imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol Chemical compound C1=CC=CC2=C(N(C(CNCC)=N3)CC(C)(C)O)C3=C(N)N=C21 FHJATBIERQTCTN-UHFFFAOYSA-N 0.000 description 2
- RXNTZIJLOZMJTM-UHFFFAOYSA-N 2-(2h-quinolin-1-yl)ethanol Chemical compound C1=CC=C2N(CCO)CC=CC2=C1 RXNTZIJLOZMJTM-UHFFFAOYSA-N 0.000 description 2
- PVVTWNMXEHROIA-UHFFFAOYSA-N 2-(3-hydroxypropyl)-1h-quinazolin-4-one Chemical compound C1=CC=C2NC(CCCO)=NC(=O)C2=C1 PVVTWNMXEHROIA-UHFFFAOYSA-N 0.000 description 2
- VYMHBQQZUYHXSS-UHFFFAOYSA-N 2-(3h-dithiol-3-yl)pyridine Chemical compound C1=CSSC1C1=CC=CC=N1 VYMHBQQZUYHXSS-UHFFFAOYSA-N 0.000 description 2
- BXJWQQWEBUICHY-UHFFFAOYSA-N 2-[[4-[[6-amino-2-(butylamino)-8-oxo-7h-purin-9-yl]methyl]benzoyl]amino]acetic acid Chemical compound C12=NC(NCCCC)=NC(N)=C2N=C(O)N1CC1=CC=C(C(=O)NCC(O)=O)C=C1 BXJWQQWEBUICHY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 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 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 241000581650 Ivesia Species 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 208000008900 Pancreatic Ductal Carcinoma Diseases 0.000 description 2
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 229960002903 benzyl benzoate Drugs 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- LNQHREYHFRFJAU-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) pentanedioate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(=O)ON1C(=O)CCC1=O LNQHREYHFRFJAU-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229940124670 gardiquimod Drugs 0.000 description 2
- 201000004528 gastrointestinal lymphoma Diseases 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000005179 haloacetyl group Chemical group 0.000 description 2
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 208000006971 mastocytoma Diseases 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 229960005558 mertansine Drugs 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- FEFIBEHSXLKJGI-UHFFFAOYSA-N methyl 2-[3-[[3-(6-amino-2-butoxy-8-oxo-7h-purin-9-yl)propyl-(3-morpholin-4-ylpropyl)amino]methyl]phenyl]acetate Chemical compound C12=NC(OCCCC)=NC(N)=C2NC(=O)N1CCCN(CC=1C=C(CC(=O)OC)C=CC=1)CCCN1CCOCC1 FEFIBEHSXLKJGI-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 108010093470 monomethyl auristatin E Proteins 0.000 description 2
- AMKBTTRWLGVRER-OFVILXPXSA-N n-[(2s)-1-[[(2s)-5-(carbamoylamino)-1-[4-(hydroxymethyl)anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-6-(2,5-dioxopyrrol-1-yl)hexanamide Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=O)C(=O)NC=1C=CC(CO)=CC=1)C(=O)CCCCCN1C(=O)C=CC1=O AMKBTTRWLGVRER-OFVILXPXSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 2
- 229960003330 pentetic acid Drugs 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
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 229960001309 procaine hydrochloride Drugs 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 239000007974 sodium acetate buffer Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- TYKASZBHFXBROF-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,5-dioxopyrrol-1-yl)acetate Chemical compound O=C1CCC(=O)N1OC(=O)CN1C(=O)C=CC1=O TYKASZBHFXBROF-UHFFFAOYSA-N 0.000 description 1
- XUDGDVPXDYGCTG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-[2-(2,5-dioxopyrrolidin-1-yl)oxycarbonyloxyethylsulfonyl]ethyl carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCCS(=O)(=O)CCOC(=O)ON1C(=O)CCC1=O XUDGDVPXDYGCTG-UHFFFAOYSA-N 0.000 description 1
- JKHVDAUOODACDU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCN1C(=O)C=CC1=O JKHVDAUOODACDU-UHFFFAOYSA-N 0.000 description 1
- NLPWBELUEANJAT-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[2-[3-(3-methyldiazirin-3-yl)propanoylamino]ethyldisulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCNC(=O)CCC1(C)N=N1 NLPWBELUEANJAT-UHFFFAOYSA-N 0.000 description 1
- PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 description 1
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 description 1
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 1
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 1
- FUOJEDZPVVDXHI-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 5-azido-2-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC=C(N=[N+]=[N-])C=C1C(=O)ON1C(=O)CCC1=O FUOJEDZPVVDXHI-UHFFFAOYSA-N 0.000 description 1
- VLARLSIGSPVYHX-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(2,5-dioxopyrrol-1-yl)hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O VLARLSIGSPVYHX-UHFFFAOYSA-N 0.000 description 1
- WCMOHMXWOOBVMZ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCN1C(=O)C=CC1=O WCMOHMXWOOBVMZ-UHFFFAOYSA-N 0.000 description 1
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 1
- IHVODYOQUSEYJJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)C(CC1)CCC1CN1C(=O)C=CC1=O IHVODYOQUSEYJJ-UHFFFAOYSA-N 0.000 description 1
- NVKZKCWZPSNZFD-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) carbonochloridate Chemical compound ClC(=O)ON1C(=O)CCC1=O NVKZKCWZPSNZFD-UHFFFAOYSA-N 0.000 description 1
- VEGGTWZUZGZKHY-GJZGRUSLSA-N (2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)-n-[4-(hydroxymethyl)phenyl]pentanamide Chemical compound NC(=O)NCCC[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)NC1=CC=C(CO)C=C1 VEGGTWZUZGZKHY-GJZGRUSLSA-N 0.000 description 1
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- OJQSISYVGFJJBY-UHFFFAOYSA-N 1-(4-isocyanatophenyl)pyrrole-2,5-dione Chemical compound C1=CC(N=C=O)=CC=C1N1C(=O)C=CC1=O OJQSISYVGFJJBY-UHFFFAOYSA-N 0.000 description 1
- SGVWDRVQIYUSRA-UHFFFAOYSA-N 1-[2-[2-(2,5-dioxopyrrol-1-yl)ethyldisulfanyl]ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CCSSCCN1C(=O)C=CC1=O SGVWDRVQIYUSRA-UHFFFAOYSA-N 0.000 description 1
- RLGNIXAVMDVPSM-UHFFFAOYSA-N 1-[4-(3,5-dichlorophenyl)sulfonylbutyl]-2-ethylimidazo[4,5-c]quinolin-4-amine Chemical compound CCC1=NC2=C(N)N=C3C=CC=CC3=C2N1CCCCS(=O)(=O)C1=CC(Cl)=CC(Cl)=C1 RLGNIXAVMDVPSM-UHFFFAOYSA-N 0.000 description 1
- CULQNACJHGHAER-UHFFFAOYSA-N 1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 CULQNACJHGHAER-UHFFFAOYSA-N 0.000 description 1
- UPNUQQDXHCUWSG-UHFFFAOYSA-N 1-[6-(4-azido-2-nitroanilino)hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC1=CC=C(N=[N+]=[N-])C=C1[N+]([O-])=O UPNUQQDXHCUWSG-UHFFFAOYSA-N 0.000 description 1
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- DEVCLHVFELRPIU-UHFFFAOYSA-N 2-(ethoxymethyl)-3h-imidazo[4,5-c]quinolin-4-amine Chemical compound NC1=NC2=CC=CC=C2C2=C1NC(COCC)=N2 DEVCLHVFELRPIU-UHFFFAOYSA-N 0.000 description 1
- RMNAJNJBCBFOKX-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanamine Chemical compound NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCN=[N+]=[N-] RMNAJNJBCBFOKX-UHFFFAOYSA-N 0.000 description 1
- QSPOQCXMGPDIHI-UHFFFAOYSA-N 2-amino-n,n-dipropyl-8-[4-(pyrrolidine-1-carbonyl)phenyl]-3h-1-benzazepine-4-carboxamide Chemical compound C1=C2N=C(N)CC(C(=O)N(CCC)CCC)=CC2=CC=C1C(C=C1)=CC=C1C(=O)N1CCCC1 QSPOQCXMGPDIHI-UHFFFAOYSA-N 0.000 description 1
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical compound SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical group NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- RFZSZPJGVHUALX-UHFFFAOYSA-N 2-butyl-1-(3-methylsulfonylpropyl)imidazo[4,5-c]quinolin-4-amine Chemical compound C1=CC=CC2=C(N(C(CCCC)=N3)CCCS(C)(=O)=O)C3=C(N)N=C21 RFZSZPJGVHUALX-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- NFYMGJSUKCDVJR-UHFFFAOYSA-N 2-propyl-[1,3]thiazolo[4,5-c]quinolin-4-amine Chemical compound C1=CC=CC2=C(SC(CCC)=N3)C3=C(N)N=C21 NFYMGJSUKCDVJR-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 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
- BIKSKRPHKQWJCW-UHFFFAOYSA-N 3,4-dibromopyrrole-2,5-dione Chemical compound BrC1=C(Br)C(=O)NC1=O BIKSKRPHKQWJCW-UHFFFAOYSA-N 0.000 description 1
- NITXODYAMWZEJY-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanehydrazide Chemical compound NNC(=O)CCSSC1=CC=CC=N1 NITXODYAMWZEJY-UHFFFAOYSA-N 0.000 description 1
- HQBUPOAKJGJGCD-UHFFFAOYSA-N 3h-imidazo[4,5-c]quinolin-4-amine Chemical compound NC1=NC2=CC=CC=C2C2=C1N=CN2 HQBUPOAKJGJGCD-UHFFFAOYSA-N 0.000 description 1
- ZMRMMAOBSFSXLN-UHFFFAOYSA-N 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanehydrazide Chemical compound C1=CC(CCCC(=O)NN)=CC=C1N1C(=O)C=CC1=O ZMRMMAOBSFSXLN-UHFFFAOYSA-N 0.000 description 1
- SHNIBVWXUOEWTA-UHFFFAOYSA-N 4-[[6-amino-2-(2-methoxyethoxy)-8-oxo-7h-purin-9-yl]methyl]benzaldehyde Chemical compound C12=NC(OCCOC)=NC(N)=C2N=C(O)N1CC1=CC=C(C=O)C=C1 SHNIBVWXUOEWTA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VFOKSTCIRGDTBR-UHFFFAOYSA-N 4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one Chemical compound C12=NC(OCCCC)=NC(N)=C2NC(=O)CN1CC(C=1)=CC=CC=1CN1CCCC1 VFOKSTCIRGDTBR-UHFFFAOYSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- KBBMDEIUGWVWEA-GVXVVHGQSA-N 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-(2-azidoethoxy)ethyl]pentanamide Chemical compound N(=[N+]=[N-])CCOCCNC(CCCC[C@@H]1SC[C@@H]2NC(N[C@@H]21)=O)=O KBBMDEIUGWVWEA-GVXVVHGQSA-N 0.000 description 1
- CMWHTSPPRPEKSH-GVXVVHGQSA-N 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-(2-azidoethyldisulfanyl)ethyl]pentanamide Chemical compound [N-]=[N+]=NCCSSCCNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@H]12 CMWHTSPPRPEKSH-GVXVVHGQSA-N 0.000 description 1
- BNCJEZWKLUBUBB-QXEWZRGKSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(2-aminoethyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCN)SC[C@@H]21 BNCJEZWKLUBUBB-QXEWZRGKSA-N 0.000 description 1
- ZWFOOMQCYIGZBE-ZOBUZTSGSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethyl]pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCOCCOCCOCCN=[N+]=[N-])SC[C@@H]21 ZWFOOMQCYIGZBE-ZOBUZTSGSA-N 0.000 description 1
- SKMJWNZZFUDLKQ-BJLQDIEVSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-[2-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethoxy]ethyl]pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCOCCOCCOCCOCC#C)SC[C@@H]21 SKMJWNZZFUDLKQ-BJLQDIEVSA-N 0.000 description 1
- PVEHVEYAPUNCCP-LNLFQRSKSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethyl]pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCOCCOCCOCCOCCN=[N+]=[N-])SC[C@@H]21 PVEHVEYAPUNCCP-LNLFQRSKSA-N 0.000 description 1
- LFMPVTVPXHNXOT-HNNXBMFYSA-N 6-amino-2-[(2s)-pentan-2-yl]oxy-9-(5-piperidin-1-ylpentyl)-7h-purin-8-one Chemical compound C12=NC(O[C@@H](C)CCC)=NC(N)=C2NC(=O)N1CCCCCN1CCCCC1 LFMPVTVPXHNXOT-HNNXBMFYSA-N 0.000 description 1
- DALMAZHDNFCDRP-VMPREFPWSA-N 9h-fluoren-9-ylmethyl n-[(2s)-1-[[(2s)-5-(carbamoylamino)-1-[4-(hydroxymethyl)anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound O=C([C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(C)C)NC1=CC=C(CO)C=C1 DALMAZHDNFCDRP-VMPREFPWSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 101100326756 Bos taurus CAPRIN1 gene Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 229940124293 CD30 monoclonal antibody Drugs 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 208000006478 Cecal Neoplasms Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229920002558 Curdlan Polymers 0.000 description 1
- 239000001879 Curdlan Substances 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 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
- UNXHWFMMPAWVPI-QWWZWVQMSA-N D-threitol Chemical compound OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical class ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000021309 Germ cell tumor Diseases 0.000 description 1
- 208000007569 Giant Cell Tumors Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 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 1
- 239000006173 Good's buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000793727 Homo sapiens Caprin-1 Proteins 0.000 description 1
- 101001125032 Homo sapiens Nucleotide-binding oligomerization domain-containing protein 1 Proteins 0.000 description 1
- 101001125026 Homo sapiens Nucleotide-binding oligomerization domain-containing protein 2 Proteins 0.000 description 1
- 101001099381 Homo sapiens Peroxisomal biogenesis factor 19 Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010021042 Hypopharyngeal cancer Diseases 0.000 description 1
- 206010056305 Hypopharyngeal neoplasm Diseases 0.000 description 1
- 208000009164 Islet Cell Adenoma Diseases 0.000 description 1
- 108010091423 L-Ala-gamma-D-Glu-meso-diaminopimelic acid Proteins 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- DUKURNFHYQXCJG-UHFFFAOYSA-N Lewis A pentasaccharide Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)OC1CO DUKURNFHYQXCJG-UHFFFAOYSA-N 0.000 description 1
- 206010062038 Lip neoplasm Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000007369 Malignant Mixed Tumor Diseases 0.000 description 1
- 206010073150 Multiple endocrine neoplasia Type 1 Diseases 0.000 description 1
- 101100059036 Mus musculus Caprin1 gene Proteins 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- 238000011789 NOD SCID mouse Methods 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 102100029424 Nucleotide-binding oligomerization domain-containing protein 1 Human genes 0.000 description 1
- 102100029441 Nucleotide-binding oligomerization domain-containing protein 2 Human genes 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
- 239000012648 POLY-ICLC Substances 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102100038883 Peroxisomal biogenesis factor 19 Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241001222774 Salmonella enterica subsp. enterica serovar Minnesota Species 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 208000009125 Sigmoid Neoplasms Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 206010041329 Somatostatinoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 206010062129 Tongue neoplasm Diseases 0.000 description 1
- ZLJJDBSDZSZVTF-LXOQPCSCSA-N Trehalose-6,6'-dibehenate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCCCCCCCCCCCC)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCCCCCCCCCCCC)O1 ZLJJDBSDZSZVTF-LXOQPCSCSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- HOOMGTNENMZAFP-NYNCVSEMSA-N [(2r,3r,5s)-2-(5-amino-2-oxo-[1,3]thiazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1C[C@@H](CO)O[C@H]1N1C(=O)SC2=CN=C(N)N=C21 HOOMGTNENMZAFP-NYNCVSEMSA-N 0.000 description 1
- KVDVZTLIGXDKKC-BHWLZUDQSA-N [4-[[(2s)-4-amino-2-[[(2s)-2-[[(2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate Chemical compound O=C([C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C)NC(C=C1)=CC=C1COC(=O)OC1=CC=C([N+]([O-])=O)C=C1 KVDVZTLIGXDKKC-BHWLZUDQSA-N 0.000 description 1
- USMYACISHVPTHK-PXLJZGITSA-N [4-[[(2s)-5-(carbamoylamino)-2-[[(2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl (4-nitrophenyl) carbonate Chemical compound O=C([C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(C)C)NC(C=C1)=CC=C1COC(=O)OC1=CC=C([N+]([O-])=O)C=C1 USMYACISHVPTHK-PXLJZGITSA-N 0.000 description 1
- 208000006336 acinar cell carcinoma Diseases 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
- 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 1
- 125000005262 alkoxyamine group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 201000010838 ascending colon cancer Diseases 0.000 description 1
- UPAZUDUZKTYFBG-HNPUZVNISA-N azane [(2S,3R,4R,5S,6R)-2,5-dihydroxy-6-[[(2R,3R,4R,5S,6R)-6-(hydroxymethyl)-5-phosphonooxy-3-[[(3R)-3-tetradecanoyloxytetradecanoyl]amino]-4-[(3R)-3-tetradecanoyloxytetradecanoyl]oxyoxan-2-yl]oxymethyl]-3-[[(3R)-3-hydroxytetradecanoyl]amino]oxan-4-yl] (3R)-3-hydroxytetradecanoate Chemical compound [NH4+].CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)N[C@H]1[C@H](OC[C@H]2O[C@H](O)[C@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H]2O)O[C@H](CO)[C@@H](OP(O)([O-])=O)[C@@H]1OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC UPAZUDUZKTYFBG-HNPUZVNISA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 201000003959 cecum carcinoma Diseases 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 229940078035 curdlan Drugs 0.000 description 1
- 235000019316 curdlan Nutrition 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- ZJVGOGQIAYMKAS-MZOCQUDTSA-N dbco-s-s-peg3-biotin Chemical compound C1C2=CC=CC=C2C#CC2=CC=CC=C2N1C(=O)CCC(=O)NCCSSCCC(=O)NCCOCCOCCOCCNC(=O)CCCC[C@H]1[C@H]2NC(=O)N[C@H]2CS1 ZJVGOGQIAYMKAS-MZOCQUDTSA-N 0.000 description 1
- PXKNJQBMPOUJER-WALFPXMSSA-N dde biotin-peg4-dbco Chemical compound O=C1CC(C)(C)CC(=O)C1=C(NCCC(=O)N1C2=CC=CC=C2C#CC2=CC=CC=C2C1)CCOCCOCCOCCOCCNC(=O)CCCC[C@H]1[C@H]2NC(=O)N[C@H]2CS1 PXKNJQBMPOUJER-WALFPXMSSA-N 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 201000003823 descending colon cancer Diseases 0.000 description 1
- COZOCMWCRHGLMP-CAXQYQEGSA-N diazo biotin-peg3-dbco Chemical compound C1C2=CC=CC=C2C#CC2=CC=CC=C2N1C(=O)CCC(=O)NCCC(C=CC1=O)=C/C1=N/NC(C=C1)=CC=C1C(=O)NCCOCCOCCOCCNC(=O)CCCC[C@H]1[C@H]2NC(=O)N[C@H]2CS1 COZOCMWCRHGLMP-CAXQYQEGSA-N 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 150000004662 dithiols Chemical class 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- IWBOPFCKHIJFMS-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl) ether Chemical compound NCCOCCOCCN IWBOPFCKHIJFMS-UHFFFAOYSA-N 0.000 description 1
- IYBKWXQWKPSYDT-UHFFFAOYSA-L ethylene glycol disuccinate bis(sulfo-N-succinimidyl) ester sodium salt Chemical compound [Na+].[Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCC(=O)OCCOC(=O)CCC(=O)ON1C(=O)C(S([O-])(=O)=O)CC1=O IYBKWXQWKPSYDT-UHFFFAOYSA-L 0.000 description 1
- YOMFVLRTMZWACQ-UHFFFAOYSA-N ethyltrimethylammonium Chemical compound CC[N+](C)(C)C YOMFVLRTMZWACQ-UHFFFAOYSA-N 0.000 description 1
- 201000007830 familial atrial fibrillation Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- QIFGMZZTJRULMA-XLPZGREQSA-N gamma-D-glutamyl-meso-diaminopimelic acid Chemical compound OC(=O)[C@@H](N)CCC[C@H](C(O)=O)NC(=O)CC[C@@H](N)C(O)=O QIFGMZZTJRULMA-XLPZGREQSA-N 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000052098 human CAPRIN1 Human genes 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 201000006866 hypopharynx cancer Diseases 0.000 description 1
- 125000005462 imide group Chemical group 0.000 description 1
- 150000003949 imides Chemical group 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 201000002529 islet cell tumor Diseases 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 201000006721 lip cancer Diseases 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000021810 malignant mixed neoplasm Diseases 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 208000022669 mucinous neoplasm Diseases 0.000 description 1
- 206010051747 multiple endocrine neoplasia Diseases 0.000 description 1
- GLLJEXIFFRQOQX-UHFFFAOYSA-N n-[2-(benzenesulfonamido)-4,5-dimethylphenyl]benzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)NC=1C=C(C)C(C)=CC=1NS(=O)(=O)C1=CC=CC=C1 GLLJEXIFFRQOQX-UHFFFAOYSA-N 0.000 description 1
- BQLBSBWCGKYXGM-UHFFFAOYSA-N n-[3-(4-amino-2-butylimidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropyl]benzamide Chemical compound CCCCC1=NC2=C(N)N=C3C=CC=CC3=C2N1CC(C)(C)CNC(=O)C1=CC=CC=C1 BQLBSBWCGKYXGM-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000014500 neuronal tumor Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 201000005443 oral cavity cancer Diseases 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 208000022102 pancreatic neuroendocrine neoplasm Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- QHTIWGZNJOYQBJ-NFDITWSSSA-N pc dbco-peg3-biotin Chemical compound C1C2=CC=CC=C2C#CC2=CC=CC=C2N1C(=O)CCNC(=O)OC(C)C1=C([N+]([O-])=O)C=C(OCCCC(=O)NCCOCCOCCOCCNC(=O)CCCC[C@H]2[C@H]3NC(=O)N[C@H]3CS2)C(OC)=C1 QHTIWGZNJOYQBJ-NFDITWSSSA-N 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- RDBMUARQWLPMNW-UHFFFAOYSA-N phosphanylmethanol Chemical compound OCP RDBMUARQWLPMNW-UHFFFAOYSA-N 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 108700002563 poly ICLC Proteins 0.000 description 1
- 229940115270 poly iclc Drugs 0.000 description 1
- 229920000889 poly(m-phenylene isophthalamide) Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- PIXCCFAIMVRUDJ-UHFFFAOYSA-N s-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethyl] ethanethioate Chemical group CC(=O)SCCOCCOCCOCCN=[N+]=[N-] PIXCCFAIMVRUDJ-UHFFFAOYSA-N 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
- 201000003825 sigmoid colon cancer Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000037968 sinus cancer Diseases 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- KTYCFZFVXSHAGH-UHFFFAOYSA-M sodium 1-[3-(3-methyldiazirin-3-yl)propanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].CC1(CCC(=O)ON2C(=O)CC(C2=O)S([O-])(=O)=O)N=N1 KTYCFZFVXSHAGH-UHFFFAOYSA-M 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- MKNJJMHQBYVHRS-UHFFFAOYSA-M sodium;1-[11-(2,5-dioxopyrrol-1-yl)undecanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCCCCCCN1C(=O)C=CC1=O MKNJJMHQBYVHRS-UHFFFAOYSA-M 0.000 description 1
- VUFNRPJNRFOTGK-UHFFFAOYSA-M sodium;1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 VUFNRPJNRFOTGK-UHFFFAOYSA-M 0.000 description 1
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- ALJRPIAYJALVFG-UHFFFAOYSA-N tert-butyl 2,2-dioxooxathiazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOS1(=O)=O ALJRPIAYJALVFG-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 201000006134 tongue cancer Diseases 0.000 description 1
- 201000010986 transverse colon cancer Diseases 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- VXNHEVDLDQWVJJ-NHJLCCERSA-N wspc biotin-peg3-dbco Chemical compound C1C2=CC=CC=C2C#CC2=CC=CC=C2N1C(=O)CCNC(=O)OC(C)C1=C([N+]([O-])=O)C=C(OCCCC(=O)NCC(C(=O)NCCOCCOCCOCCNC(=O)CCCC[C@H]2[C@H]3NC(=O)N[C@H]3CS2)S(O)(=O)=O)C(OC)=C1 VXNHEVDLDQWVJJ-NHJLCCERSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
(1)配列番号2〜30のうち偶数の配列番号のいずれかで表されるアミノ酸配列又は、該アミノ酸配列と80%以上の配列同一性を有するアミノ酸配列を有するCAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメントと、免疫活性化因子が結合されてなるコンジュゲート。
(2)前記抗体又はそのフラグメントが、配列番号31〜35、296〜299、308、309のいずれかで表されるアミノ酸配列あるいは該アミノ酸配列と80%以上の配列同一性を有するアミノ酸配列を有するCAPRIN−1タンパク質の部分ポリペプチドと免疫学的反応性を有する、(1)に記載のコンジュゲート。
(3)前記抗体がモノクローナル抗体又はポリクローナル抗体である、(1)又は(2)に記載のコンジュゲート。
(4)前記抗体又はそのフラグメントが以下の(A)〜(M)のいずれかである、(1)〜(3)のいずれかに記載のコンジュゲート
(A)配列番号36、37及び38の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号40、41及び42の相補性決定領域(それぞれCDR1、CDR2及びCD3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(B)配列番号44、45及び46の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号48、49及び50の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(C)配列番号52、53及び54の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号56、57及び58の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(D)配列番号60、61及び62の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号64、65及び66の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(E)配列番号170、171及び172の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号173、174及び175の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(F)配列番号176、177及び178の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号179、180及び181の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(G)配列番号182、183及び184の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号185、186及び187の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(H)配列番号188、189及び190の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号191、192及び193の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(I)配列番号146、147及び148の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号149、150及び151の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(J)配列番号272、273及び274の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号275、276及び277の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(K)配列番号290、291及び292の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号293、294及び295の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(L)配列番号301、302及び303の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号305、306及び307の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(M)配列番号134、135及び136の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号137、138及び139の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(5)前記抗体又はそのフラグメントが以下の(a)〜(ak)のいずれかである、(1)〜(4)のいずれかに記載のコンジュゲート。
(a)重鎖可変領域が配列番号39のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号43のアミノ酸配列を含んでなる抗体又はそのフラグメント
(b)重鎖可変領域が配列番号47のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号51のアミノ酸配列を含んでなる抗体又はそのフラグメント
(c)重鎖可変領域が配列番号55のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号59のアミノ酸配列を含んでなる抗体又はそのフラグメント
(d)重鎖可変領域が配列番号63のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号67のアミノ酸配列を含んでなる抗体又はそのフラグメント
(e)重鎖可変領域が配列番号68のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号69のアミノ酸配列を含んでなる抗体又はそのフラグメント
(f)重鎖可変領域が配列番号70のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号71のアミノ酸配列を含んでなる抗体又はそのフラグメント
(g)重鎖可変領域が配列番号72のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号73のアミノ酸配列を含んでなる抗体又はそのフラグメント
(h)重鎖可変領域が配列番号74のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号75のアミノ酸配列を含んでなる抗体又はそのフラグメント
(i)重鎖可変領域が配列番号76のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号77のアミノ酸配列を含んでなる抗体又はそのフラグメント
(j)重鎖可変領域が配列番号78のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号79のアミノ酸配列を含んでなる抗体又はそのフラグメント
(k)重鎖可変領域が配列番号80のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号81のアミノ酸配列を含んでなる抗体又はそのフラグメント
(l)重鎖可変領域が配列番号82のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号83のアミノ酸配列を含んでなる抗体又はそのフラグメント
(m)重鎖可変領域が配列番号84のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号85のアミノ酸配列を含んでなる抗体又はそのフラグメント
(n)重鎖可変領域が配列番号86のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号87のアミノ酸配列を含んでなる抗体又はそのフラグメント
(o)重鎖可変領域が配列番号88のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号89のアミノ酸配列を含んでなる抗体又はそのフラグメント
(p)重鎖可変領域が配列番号90のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号91のアミノ酸配列を含んでなる抗体又はそのフラグメント
(q)重鎖可変領域が配列番号92のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号93のアミノ酸配列を含んでなる抗体又はそのフラグメント
(r)重鎖可変領域が配列番号94のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号95のアミノ酸配列を含んでなる抗体又はそのフラグメント
(s)重鎖可変領域が配列番号96のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号97のアミノ酸配列を含んでなる抗体又はそのフラグメント
(t)重鎖可変領域が配列番号98のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号99のアミノ酸配列を含んでなる抗体又はそのフラグメント
(u)重鎖可変領域が配列番号100のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号101のアミノ酸配列を含んでなる抗体又はそのフラグメント
(v)重鎖可変領域が配列番号102のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号103のアミノ酸配列を含んでなる抗体又はそのフラグメント
(w)重鎖可変領域が配列番号104のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号105のアミノ酸配列を含んでなる抗体又はそのフラグメント
(x)重鎖可変領域が配列番号106のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号107のアミノ酸配列を含んでなる抗体又はそのフラグメント
(y)重鎖可変領域が配列番号108のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号109のアミノ酸配列を含んでなる抗体又はそのフラグメント
(z)重鎖可変領域が配列番号110のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号111のアミノ酸配列を含んでなる抗体又はそのフラグメント
(aa)重鎖可変領域が配列番号112のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号113のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ab)重鎖可変領域が配列番号114のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号115のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ac)重鎖可変領域が配列番号116のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号117のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ad)重鎖可変領域が配列番号118のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号119のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ae)重鎖可変領域が配列番号120のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号121のアミノ酸配列を含んでなる抗体又はそのフラグメント
(af)重鎖可変領域が配列番号122のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号123のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ag)重鎖可変領域が配列番号124のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号125のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ah)重鎖可変領域が配列番号126のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号127のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ai)重鎖可変領域が配列番号128のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号129のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ai)重鎖可変領域が配列番号130のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号131のアミノ酸配列を含んでなる抗体又はそのフラグメント
(aj)重鎖可変領域が配列番号132のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号133のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ak)重鎖可変領域が配列番号300のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号304のアミノ酸配列を含んでなる抗体又はそのフラグメント
(6)前記抗体が、ヒト抗体、ヒト化抗体、キメラ抗体、単鎖抗体である、(1)〜(5)のいずれかに記載のコンジュゲート。
(7)前記免疫活性化因子が、Toll様受容体(TLR)、NOD様受容体(NLR)、RIG様受容体、C型レクチン受容体(CLR)に結合するリガンド又はアゴニストである、(1)〜(6)のいずれかに記載のコンジュゲート。
(8)前記Toll様受容体(TLR)が、TLR2、TLR3、TLR4、TLR5、TLR7、TLR8、TLR9又はTLR10である、(7)に記載のコンジュゲート。
(9)前記Toll様受容体(TLR)に結合するリガンド又はアゴニスト又はその誘導体が以下の(i)〜(vii)のいずれかである、(7)又は(8)項に記載のコンジュゲート。
(i)ペプチドグリカン、リポタンパク質、リポポリサッカライド及びザイモザンからななる群から選択されるTLR2に結合するリガンド又はアゴニスト
(ii)Poly(I:C)及びpoly(A:U)からなる群から選択されるTLR3に結合するリガンド又はアゴニスト
(iii)リポポリサッカライド(LPS)、HSP60、RS09及びMPLAからなる群から選択されるTLR4に結合するリガンド又はアゴニスト
(iv)フラジェリン及びFLAからなる群から選択されるTLR5に結合するリガンド又はアゴニスト
(v)イミダゾキノリン類化合物及び一重鎖RNAからなる群から選択されるTRL7又は8に結合するリガンド又はアゴニスト
(vi)バクテリアDNA、非メチル化CpG DNA、hemozorin、ODN1585、ODN1668、ODN1668及びODN1826からなる群から選択されるTRL9に結合するリガンド又はアゴニスト
(vii)profilin及びuropathogenicバクテリアからなる群から選択されるTRL10に結合するリガンド又はアゴニスト
(10)前記抗体又はそのフラグメントと前記免疫活性化因子がリンカーを介して結合する、(1)〜(9)のいずれかに記載のコンジュゲート。
(11)(1)〜(10)のいずれかに記載のコンジュゲートを有効成分として含む、癌の治療及び/又は予防のための医薬組成物。
(12)前記癌がCAPRIN−1タンパク質を細胞膜表面に発現する癌である、(11)に記載の医薬組成物。
(13)前記癌が、乳癌、腎癌、膵臓癌、大腸癌、肺癌、脳腫瘍、胃癌、子宮癌、卵巣癌、前立腺癌、膀胱癌、食道癌、白血病、リンパ腫、肝臓癌、胆嚢癌、肉腫、肥満細胞腫、メラノーマ、副腎皮質癌、ユーイング腫瘍、ホジキンリンパ腫、中皮腫、多発性骨髄腫、睾丸癌、甲状腺癌及び頭頸部癌からなる群から選択される癌である、(11)又は(12)に記載の医薬組成物。
(14)(1)〜(10)のいずれかに記載のコンジュゲート、(11)〜(13)のいずれかに記載の医薬組成物を被験者に投与することを含む、癌の治療及び/又は予防方法。
本発明で用いられる抗CAPRIN−1抗体と免疫学的反応性を有する、配列番号2〜30のうち偶数の配列番号のいずれかで表されるアミノ酸配列を有するCAPRIN−1タンパク質のうち、配列番号6、8、10、12及び14で示されるアミノ酸配列はイヌのCAPRIN−1タンパク質のアミノ酸配列であり、配列番号2及び4で示されるアミノ酸配列はヒトのCAPRIN−1タンパク質のアミノ酸配列であり、配列番号16で示されるアミノ酸配列はウシのCAPRIN−1タンパク質のアミノ酸配列であり、配列番号18で示されるアミノ酸配列はウマのCAPRIN−1タンパク質のアミノ酸配列であり、配列番号20〜28で示されるアミノ酸配列はマウスのCAPRIN−1タンパク質のアミノ酸配列であり、配列番号30で示されるアミノ酸配列はニワトリのCAPRIN−1タンパク質のアミノ酸配列である。
本発明に係る免疫活性化因子は、ここでは各種免疫細胞を活性化する因子であり、該細胞の免疫機能を維持、増強しうる天然化合物、核酸あるいは天然化合物を意味する。ここでいう「免疫細胞」とは、Tリンパ球、Bリンパ球、NK細胞、単球、樹状細胞、顆粒球、マクロファージ、骨髄由来抑制性細胞、Langerhance細胞およびその前駆細胞群、腫瘍内に存在する前記免疫細胞群である。
本発明において、抗CAPRIN−1抗体と免疫活性化因子のコンジュゲートにおける抗CAPRIN−1抗体と免疫活性化因子の結合の形態は、癌に対する抗腫瘍活性を維持しうる形態であれば特に制限はないが、抗CAPRIN−1抗体と免疫活性化因子との間にリンカー構造が形成される結合の形態であることが好ましい。
リンカーが結合した抗体を含んだ組成物を得るためには、例えばゲル濾過クロマトグラフィーなどに供することで、リンカーを結合する前の抗体と比較して、より高分子化したピークを分取することで得ることできる。
本発明の抗CAPRIN−1抗体と免疫活性化因子とのコンジュゲートは、インビトロあるいはインビボで、細胞障害活性を有する。よって本発明のコンジュゲートの抗腫瘍効果は、癌に対する細胞障害活性を調べることによって知ることが可能である。細胞障害活性は、癌を有する生体へコンジュゲートを投与し、投与後の腫瘍の大きさを計測して、癌の大きさを経時的に調べる事によって評価できる。本発明の抗腫瘍効果は、生存率を調べることによっても評価できる。また、サイトカインあるいはケモカインの産生能を調べる事によっても評価できる。本発明のコンジュゲートの抗腫瘍効果は、さらに癌の予防、転移の予防あるいは再発の予防を調べることによって知ることができる。
本発明の癌の治療及び/又は予防のための医薬組成物の標的は、CAPRIN−1タンパク質を発現する癌(細胞)であれば特に限定されない。
コンジュゲートに用いるCAPRIN−1タンパク質と免疫学的反応性を有する抗CAPRIN−1ポリクローナル抗体は、WO2010/016526の実施例3に従って作製した配列番号2および配列番号4で示されるヒトCAPRIN−1組換えタンパク質1mgを等容量の不完全フロイントアジュバント(IFA)溶液と混合し、これを2週間毎に4回、ウサギの皮下に投与を行った。その後血液を採取し、ポリクローナル抗体を含む抗血清を得た。得られた抗血清を、プロテインG担体(GEヘルスケアバイオサイエンス)を用いて精製し、CAPRIN−1タンパク質に対するポリクローナル抗体(抗CAPRIN−1ポリクローナル抗体#1)を得た。また、抗原を投与していないウサギの血清を上記と同様にしてプロテインG担体を用いて精製したものをウサギコントロール抗体とした。
本発明のコンジュゲートに用いる抗CAPRIN−1モノクローナル抗体は以下のものを用いた。
実施例1に記載の抗CAPRIN−1ポリクローナル抗体#1〜#6と免疫活性化因子であるResiquimodとのコンジュゲートを、マレイミドカプロイル−バリン−シトルリン−p−アミノベンジルオキシカルボニル(MC−val−Cit−PAB−PNP)をリンカーとして用いて作製した。本コンジュゲートは、WO2014/012479に記載されている方法を参照した。
実施例1に記載の抗CAPRIN−1ポリクローナル抗体と免疫活性化因子とのコンジュゲートを以下の方法にて作製した。免疫活性化因子としては、Resiqiomodにある三級水酸基へ2炭素増炭してアミノ基を付けたResiquimod誘導体である1−(2(2−Aminoethoxy)−2−methylpropyl)−2−(ethoxymethyl)−1H−imidazo[4,5−c]quinolin−4−amineを定法に従い合成し、作製した。
実施例3にて作製した、コンジュゲート1〜コンジュゲート14、コンジュゲート45〜コンジュゲート110ならびに実施例4にて作製したコンジュゲート15〜コンジュゲート28、コンジュゲート111〜コンジュゲート176のCAPRIN−1タンパク質への特異的反応性と、CAPRIN−1タンパク質が発現しているヒト癌細胞ならびにマウス癌細胞の細胞膜表面に反応性を示すことを評価した。
次に、実施例3ならびに実施例4にて作製した、抗CAPRIN−1ポリクローナル抗体#1〜#6を用いて作製したコンジュゲート1〜6ならびにコンジュゲート15〜20と、抗CAPRIN−1モノクローナル抗体を用いて作製したコンジュゲート7〜14、コンジュゲート21〜28の担癌マウス生体内における抗腫瘍効果を評価した。
実施例3ならびに4にて作製した抗CAPRIN−1抗体と免疫活性化因子とのコンジュゲート(コンジュゲート1〜28)の担癌マウス生体内における抗腫瘍効果を評価した。
抗CAPRIN−1モノクローナル抗体の重鎖可変領域とマウスIgGの重鎖定常領域を有する重鎖と、抗CAPRIN−1モノクローナル抗体の軽鎖可変領域とマウスIgGの軽鎖定常領域からなるマウスキメラ抗体を作製し、実施例3と同様の方法にて免疫活性化因子であるResiquimodとのコンジュゲートを作製した。また、前記マウスキメラ抗体を作製し、実施例4と同様の方法にて前記Resiquimodの誘導体とマウスキメラ抗体とのコンジュゲートを作製した。
実施例8にて作製した、マウスキメラ抗CAPRIN−1モノクローナル抗体と免疫活性化因子とのコンジュゲート(コンジュゲート29〜36、コンジュゲート177〜242)の抗体の担癌マウス生体内における抗腫瘍効果を評価した。
実施例4にて作製した、抗CAPRIN−1モノクローナル抗体を用いて作製したコンジュゲート7〜14、コンジュゲート21〜28、コンジュゲート45〜179と、既存の癌に対する抗体医薬トラスツマブを用いて実施例4と同様の方法を用いて作製したトラスツマブコンジュゲートならびにトラスツマブとの担癌マウス生体内における抗腫瘍効果を比較した。
実施例2に記載の抗CAPRIN−1モノクローナル抗体であるヒト化抗体#1〜#8について、それぞれ免疫活性化因子DSR−6434(6−Amino−2(butylamino)−9−[[6−[2−(dimethylamino)ethoxy]−3pyridinyl]methyl]−7,9−dihydro−8H−purin−8−one)とのコンジュゲート(コンジュゲート37〜44)を作製した。具体的には、実施例4に記載の方法に準じて、まずはDSR−6434のアミノ基を介してスクシイミジル4−(N−マレイミドメチル)シクロヘキサン−1−カルボキレート(SMCC)との縮合体を合成したうえで、ヒト化抗体#1〜#8のそれぞれと免疫活性化因子RSR−6434とのコンジュゲートである各コンジュゲート37〜44を含む溶液を得た。
Claims (14)
- 配列番号2〜30のうち偶数の配列番号のいずれかで表されるアミノ酸配列又は、該アミノ酸配列と80%以上の配列同一性を有するアミノ酸配列を有するCAPRIN−1タンパク質、と免疫学的反応性を有する抗体又はそのフラグメントと、免疫活性化因子が結合されてなるコンジュゲート。
- 前記抗体又はそのフラグメントが、配列番号31〜35、296〜299、308、309のいずれかで表されるアミノ酸配列、あるいは該アミノ酸配列と80%以上の配列同一性を有するアミノ酸配列を有するCAPRIN−1タンパク質の部分ポリペプチドと免疫学的反応性を有する、請求項1に記載のコンジュゲート。
- 前記抗体がモノクローナル抗体又はポリクローナル抗体である、請求項1又は2に記載のコンジュゲート。
- 前記抗体又はそのフラグメントが以下の(A)〜(M)のいずれかである、請求項1〜3のいずれか1項に記載のコンジュゲート
(A)配列番号36、37及び38の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号40、41及び42の相補性決定領域(それぞれCDR1、CDR2及びCD3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(B)配列番号44、45及び46の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号48、49及び50の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(C)配列番号52、53及び54の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号56、57及び58の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(D)配列番号60、61及び62の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号64、65及び66の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はフラグメント
(E)配列番号170、171及び172の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号173、174及び175の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(F)配列番号176、177及び178の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号179、180及び181の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(G)配列番号182、183及び184の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号185、186及び187の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(H)配列番号188、189及び190の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号191、192及び193の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(I)配列番号146、147及び148の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号149、150及び151の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(J)配列番号272、273及び274の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号275、276及び277の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(K)配列番号290、291及び292の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号293、294及び295の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(L)配列番号301、302及び303の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号305、306及び307の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント
(M)配列番号134、135及び136の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む重鎖可変領域と配列番号137、138及び139の相補性決定領域(それぞれCDR1、CDR2及びCDR3)を含む軽鎖可変領域とを含み、かつ、CAPRIN−1タンパク質と免疫学的反応性を有する抗体又はそのフラグメント - 前記抗体又はそのフラグメントが以下の(a)〜(ak)のいずれかである、請求項1〜4のいずれか1項に記載のコンジュゲート。
(a)重鎖可変領域が配列番号39のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号43のアミノ酸配列を含んでなる抗体又はそのフラグメント
(b)重鎖可変領域が配列番号47のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号51のアミノ酸配列を含んでなる抗体又はそのフラグメント
(c)重鎖可変領域が配列番号55のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号59のアミノ酸配列を含んでなる抗体又はそのフラグメント
(d)重鎖可変領域が配列番号63のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号67のアミノ酸配列を含んでなる抗体又はそのフラグメント
(e)重鎖可変領域が配列番号68のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号69のアミノ酸配列を含んでなる抗体又はそのフラグメント
(f)重鎖可変領域が配列番号70のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号71のアミノ酸配列を含んでなる抗体又はそのフラグメント
(g)重鎖可変領域が配列番号72のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号73のアミノ酸配列を含んでなる抗体又はそのフラグメント
(h)重鎖可変領域が配列番号74のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号75のアミノ酸配列を含んでなる抗体又はそのフラグメント
(i)重鎖可変領域が配列番号76のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号77のアミノ酸配列を含んでなる抗体又はそのフラグメント
(j)重鎖可変領域が配列番号78のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号79のアミノ酸配列を含んでなる抗体又はそのフラグメント
(k)重鎖可変領域が配列番号80のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号81のアミノ酸配列を含んでなる抗体又はそのフラグメント
(l)重鎖可変領域が配列番号82のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号83のアミノ酸配列を含んでなる抗体又はそのフラグメント
(m)重鎖可変領域が配列番号84のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号85のアミノ酸配列を含んでなる抗体又はそのフラグメント
(n)重鎖可変領域が配列番号86のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号87のアミノ酸配列を含んでなる抗体又はそのフラグメント
(o)重鎖可変領域が配列番号88のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号89のアミノ酸配列を含んでなる抗体又はそのフラグメント
(p)重鎖可変領域が配列番号90のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号91のアミノ酸配列を含んでなる抗体又はそのフラグメント
(q)重鎖可変領域が配列番号92のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号93のアミノ酸配列を含んでなる抗体又はそのフラグメント
(r)重鎖可変領域が配列番号94のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号95のアミノ酸配列を含んでなる抗体又はそのフラグメント
(s)重鎖可変領域が配列番号96のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号97のアミノ酸配列を含んでなる抗体又はそのフラグメント
(t)重鎖可変領域が配列番号98のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号99のアミノ酸配列を含んでなる抗体又はそのフラグメント
(u)重鎖可変領域が配列番号100のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号101のアミノ酸配列を含んでなる抗体又はそのフラグメント
(v)重鎖可変領域が配列番号102のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号103のアミノ酸配列を含んでなる抗体又はそのフラグメント
(w)重鎖可変領域が配列番号104のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号105のアミノ酸配列を含んでなる抗体又はそのフラグメント
(x)重鎖可変領域が配列番号106のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号107のアミノ酸配列を含んでなる抗体又はそのフラグメント
(y)重鎖可変領域が配列番号108のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号109のアミノ酸配列を含んでなる抗体又はそのフラグメント
(z)重鎖可変領域が配列番号110のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号111のアミノ酸配列を含んでなる抗体又はそのフラグメント
(aa)重鎖可変領域が配列番号112のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号113のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ab)重鎖可変領域が配列番号114のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号115のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ac)重鎖可変領域が配列番号116のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号117のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ad)重鎖可変領域が配列番号118のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号119のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ae)重鎖可変領域が配列番号120のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号121のアミノ酸配列を含んでなる抗体又はそのフラグメント
(af)重鎖可変領域が配列番号122のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号123のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ag)重鎖可変領域が配列番号124のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号125のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ah)重鎖可変領域が配列番号126のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号127のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ai)重鎖可変領域が配列番号128のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号129のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ai)重鎖可変領域が配列番号130のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号131のアミノ酸配列を含んでなる抗体又はそのフラグメント
(aj)重鎖可変領域が配列番号132のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号133のアミノ酸配列を含んでなる抗体又はそのフラグメント
(ak)重鎖可変領域が配列番号300のアミノ酸配列を含み、かつ、軽鎖可変領域が配列番号304のアミノ酸配列を含んでなる抗体又はそのフラグメント。 - 前記抗体が、ヒト抗体、ヒト化抗体、キメラ抗体又は単鎖抗体である、請求項1〜5のいずれか1項に記載のコンジュゲート。
- 前記免疫活性化因子が、Toll様受容体(TLR)、NOD様受容体(NLR)、RIG様受容体又はC型レクチン受容体(CLR)に結合するリガンド又はアゴニストである、請求項1〜6のいずれか1項に記載のコンジュゲート。
- 前記Toll様受容体(TLR)が、TLR2、TLR3、TLR4、TLR5、TLR7、TLR8、TLR9又はTLR10に結合するリガンド又はアゴニストである、請求項7に記載のコンジュゲート。
- 前記Toll様受容体(TLR)に結合するリガンド又はアゴニストが、以下の(i)〜(vii)のいずれかである、請求項7又は8に記載のコンジュゲート。
(i)ペプチドグリカン、リポタンパク質、リポポリサッカライド及びザイモザンからななる群から選択されるTLR2に結合するリガンド又はアゴニスト
(ii)Poly(I:C)及びpoly(A:U)からなる群から選択されるTLR3に結合するリガンド又はアゴニスト
(iii)リポポリサッカライド(LPS)、HSP60、RS09及びMPLAからなる群から選択されるTLR4に結合するリガンド又はアゴニスト
(iv)フラジェリン及びFLAからなる群から選択されるTLR5に結合するリガンド又はアゴニスト
(v)イミダゾキノリン類化合物及び一重鎖RNAからなる群から選択されるTRL7又は8に結合するリガンド又はアゴニスト
(vi)バクテリアDNA、非メチル化CpG DNA、hemozorin、ODN1585、ODN1668、ODN1668及びODN1826からなる群から選択されるTRL9に結合するリガンド又はアゴニスト
(vii)profilin及びuropathogenicバクテリアからなる群から選択されるTRL10に結合するリガンド又はアゴニスト - 前記抗体又はそのフラグメントと前記免疫活性化因子がリンカーを介して結合する、請求項1〜9のいずれか1項に記載のコンジュゲート。
- 請求項1〜10のいずれか1項に記載のコンジュゲートを有効成分として含む、癌の治療及び/又は予防のための医薬組成物。
- 前記癌がCAPRIN−1タンパク質を細胞膜表面に発現する癌である、請求項11に記載の医薬組成物。
- 前記癌が、乳癌、腎癌、膵臓癌、大腸癌、肺癌、脳腫瘍、胃癌、子宮癌、卵巣癌、前立腺癌、膀胱癌、食道癌、白血病、リンパ腫、肝臓癌、胆嚢癌、肉腫、肥満細胞腫、メラノーマ、副腎皮質癌、ユーイング腫瘍、ホジキンリンパ腫、中皮腫、多発性骨髄腫、睾丸癌、甲状腺癌、頭頸部癌である、請求項11又は12に記載の医薬組成物。
- 請求項1〜10のいずれか1項に記載のコンジュゲート、請求項11〜13のいずれか1項に記載の医薬組成物を、被験者に投与することを含む、癌の治療及び/又は予防方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2023000134A JP2023026581A (ja) | 2016-10-28 | 2023-01-04 | 癌の治療及び/又は予防用医薬組成物 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016211376 | 2016-10-28 | ||
JP2016211376 | 2016-10-28 | ||
PCT/JP2017/038986 WO2018079740A1 (ja) | 2016-10-28 | 2017-10-27 | 癌の治療及び/又は予防用医薬組成物 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023000134A Division JP2023026581A (ja) | 2016-10-28 | 2023-01-04 | 癌の治療及び/又は予防用医薬組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2018079740A1 true JPWO2018079740A1 (ja) | 2019-09-19 |
JP7206590B2 JP7206590B2 (ja) | 2023-01-18 |
Family
ID=62023668
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017563359A Active JP7206590B2 (ja) | 2016-10-28 | 2017-10-27 | 癌の治療及び/又は予防用医薬組成物 |
JP2023000134A Pending JP2023026581A (ja) | 2016-10-28 | 2023-01-04 | 癌の治療及び/又は予防用医薬組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023000134A Pending JP2023026581A (ja) | 2016-10-28 | 2023-01-04 | 癌の治療及び/又は予防用医薬組成物 |
Country Status (11)
Country | Link |
---|---|
US (1) | US20200054762A1 (ja) |
EP (1) | EP3533466A4 (ja) |
JP (2) | JP7206590B2 (ja) |
KR (2) | KR20190075921A (ja) |
CN (1) | CN109890417A (ja) |
AU (1) | AU2017348734A1 (ja) |
BR (1) | BR112019008335A2 (ja) |
CA (1) | CA3041979A1 (ja) |
MX (1) | MX2019004779A (ja) |
RU (1) | RU2766586C2 (ja) |
WO (1) | WO2018079740A1 (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101638490B1 (ko) * | 2008-08-05 | 2016-07-11 | 도레이 카부시키가이샤 | 암의 치료 및 예방용 의약 조성물 |
KR20230149857A (ko) | 2016-07-07 | 2023-10-27 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | 항체-애쥬번트 접합체 |
JP7342701B2 (ja) * | 2018-03-30 | 2023-09-12 | 東レ株式会社 | 癌の治療及び/又は予防用医薬組成物 |
KR20220004634A (ko) | 2019-03-15 | 2022-01-11 | 볼트 바이오테라퓨틱스 인코퍼레이티드 | Her2를 표적으로 하는 면역접합체 |
BR112021025034A2 (pt) | 2019-06-13 | 2022-04-26 | Bolt Biotherapeutics Inc | Imunoconjugado, composto aminobenzazepina-ligante, composição farmacêutica, métodos para tratar câncer e para preparar um imunoconjugado e uso de um imunoconjugado |
MX2022003740A (es) | 2019-09-30 | 2022-05-02 | Bolt Biotherapeutics Inc | Inmunoconjugados de aminobenzazepina unidos a amida y usos de estos. |
WO2021081407A1 (en) | 2019-10-25 | 2021-04-29 | Bolt Biotherapeutics, Inc. | Thienoazepine immunoconjugates, and uses thereof |
JP2023524271A (ja) | 2020-05-08 | 2023-06-09 | ボルト バイオセラピューティクス、インコーポレーテッド | エラスターゼ-基質ペプチドリンカーイムノコンジュゲート、及びそれらの使用 |
US20230263903A1 (en) | 2020-08-13 | 2023-08-24 | Bolt Biotherapeutics, Inc. | Pyrazoloazepine immunoconjugates, and uses thereof |
KR20240051956A (ko) * | 2021-09-03 | 2024-04-22 | 도레이 카부시키가이샤 | 암의 치료 및/또는 예방용 의약 조성물 |
WO2023076599A1 (en) | 2021-10-29 | 2023-05-04 | Bolt Biotherapeutics, Inc. | Tlr agonist immunoconjugates with cysteine-mutant antibodies, and uses thereof |
WO2024005123A1 (ja) * | 2022-06-30 | 2024-01-04 | 東レ株式会社 | 癌の治療及び/又は予防用医薬組成物 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010016525A1 (ja) * | 2008-08-05 | 2010-02-11 | 東レ株式会社 | 免疫誘導剤 |
WO2010095463A1 (ja) * | 2009-02-20 | 2010-08-26 | 有限会社メイショウ | 免疫増強組成物及びそれを製造する方法 |
WO2013147169A1 (ja) * | 2012-03-30 | 2013-10-03 | 東レ株式会社 | 肝臓癌の治療及び/又は予防用医薬組成物 |
WO2015020212A1 (ja) * | 2013-08-09 | 2015-02-12 | 東レ株式会社 | 癌の治療及び/又は予防用医薬組成物 |
JP2015524399A (ja) * | 2012-07-18 | 2015-08-24 | シャンハイ バーディー バイオテック インコーポレイテッド | 標的免疫療法のための化合物 |
JP2016516798A (ja) * | 2013-04-22 | 2016-06-09 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ヒトのcsf−1rに対する抗体及びtlr9アゴニストの併用療法 |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
CA2194907A1 (en) | 1994-07-13 | 1996-02-01 | Kouji Matsushima | Reshaped human antibody against human interleukin-8 |
US6677436B1 (en) | 1998-04-03 | 2004-01-13 | Chugai Seiyaku Kabushiki Kaisha | Humanized antibody against human tissue factor (TF) and process of production of the humanized antibody |
ATE458007T1 (de) | 1998-04-20 | 2010-03-15 | Glycart Biotechnology Ag | Glykosylierungs-engineering von antikörpern zur verbesserung der antikörperabhängigen zellvermittelten zytotoxizität |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
EP2264166B1 (en) | 1999-04-09 | 2016-03-23 | Kyowa Hakko Kirin Co., Ltd. | Method for controlling the activity of immunologically functional molecule |
FR2807767B1 (fr) | 2000-04-12 | 2005-01-14 | Lab Francais Du Fractionnement | Anticorps monoclonaux anti-d |
EP1545613B9 (en) | 2002-07-31 | 2012-01-25 | Seattle Genetics, Inc. | Auristatin conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
JP2006524039A (ja) | 2003-01-09 | 2006-10-26 | マクロジェニクス,インコーポレーテッド | 変異型Fc領域を含む抗体の同定および作製ならびにその利用法 |
US8388955B2 (en) | 2003-03-03 | 2013-03-05 | Xencor, Inc. | Fc variants |
DE10359795A1 (de) | 2003-12-19 | 2005-07-21 | Bayer Technology Services Gmbh | Strangverdampfervorrichtung |
US8951528B2 (en) | 2006-02-22 | 2015-02-10 | 3M Innovative Properties Company | Immune response modifier conjugates |
KR101638490B1 (ko) | 2008-08-05 | 2016-07-11 | 도레이 카부시키가이샤 | 암의 치료 및 예방용 의약 조성물 |
CA2766405A1 (en) | 2009-06-22 | 2011-01-13 | Medimmune, Llc | Engineered fc regions for site-specific conjugation |
EP2480671B8 (en) | 2009-09-22 | 2015-10-28 | ProBioGen AG | Process for producing molecules containing specialized glycan structures |
PL2532365T3 (pl) * | 2010-02-04 | 2016-12-30 | Kompozycja farmaceutyczna do leczenia i/lub zapobiegania nowotworowi | |
HUE030742T2 (en) | 2010-02-04 | 2017-06-28 | Toray Industries | A pharmaceutical composition for the treatment and / or prevention of cancer |
US8911740B2 (en) | 2010-02-04 | 2014-12-16 | Toray Industries, Inc. | Pharmaceutical composition for treating and/or preventing cancer |
PT2532743E (pt) | 2010-02-04 | 2015-08-04 | Toray Industries | Composição farmacêutica para o tratamento e/ou a prevenção de cancro |
RU2567657C2 (ru) * | 2010-02-04 | 2015-11-10 | Торэй Индастриз, Инк. | Фармацевтическая композиция для лечения и/или профилактики рака |
HUE040012T2 (hu) | 2010-02-04 | 2019-02-28 | Toray Industries | Gyógyászati ágens rák kezelésére és/vagy megelõzésére |
JP2013523098A (ja) | 2010-03-29 | 2013-06-17 | ザイムワークス,インコーポレイテッド | 強化又は抑制されたエフェクター機能を有する抗体 |
CN103118678A (zh) * | 2010-07-16 | 2013-05-22 | 约翰斯·霍普金斯大学 | 用于癌症免疫治疗的方法和组合物 |
AU2012290949B2 (en) | 2011-08-04 | 2017-03-02 | Toray Industries, Inc. | Pharmaceutical composition for treatment and/or prevention of pancreatic cancer |
RU2610428C2 (ru) | 2011-08-04 | 2017-02-10 | Торэй Индастриз, Инк. | Фармацевтическая композиция для лечения и/или профилактики злокачественной опухоли |
CN103717740B (zh) | 2011-08-04 | 2015-10-21 | 东丽株式会社 | 癌的治疗和/或预防用药物组合物 |
BR112014002621B1 (pt) | 2011-08-04 | 2022-09-20 | Toray Industries, Inc | Anticorpo, ou seu fragmento, composição farmacêutica, uso de um anticorpo e uso de uma composição farmacêutica |
KR101980554B1 (ko) | 2011-08-04 | 2019-05-21 | 도레이 카부시키가이샤 | 암의 치료 및/또는 예방용 의약 조성물 |
EP2740798B1 (en) | 2011-08-04 | 2016-12-07 | Toray Industries, Inc. | Cancer treatment and/or prevention drug composition |
ES2749672T3 (es) | 2012-02-21 | 2020-03-23 | Toray Industries | Composición farmacéutica para tratar y/o prevenir el cáncer |
PL2824114T3 (pl) | 2012-02-21 | 2019-11-29 | Toray Industries | Kompozycja farmaceutyczna do leczenia nowotworu |
HUE044611T2 (hu) | 2012-02-21 | 2019-11-28 | Toray Industries | Gyógyászati készítmény rák kezelésére |
PL2818483T3 (pl) | 2012-02-21 | 2018-01-31 | Toray Industries | Kompozycja lecznicza do leczenia i/lub zapobiegania nowotworowi |
PL2832366T3 (pl) | 2012-03-30 | 2018-04-30 | Toray Industries, Inc. | Kompozycja farmaceutyczna do leczenia i/lub zapobiegania rakowi pęcherzyka żółciowego |
AU2015205756A1 (en) | 2014-01-10 | 2016-07-21 | Birdie Biopharmaceuticals Inc. | Compounds and compositions for treating EGFR expressing tumors |
-
2017
- 2017-10-27 KR KR1020197011516A patent/KR20190075921A/ko active Application Filing
- 2017-10-27 KR KR1020247000032A patent/KR20240005247A/ko active Application Filing
- 2017-10-27 EP EP17864888.7A patent/EP3533466A4/en active Pending
- 2017-10-27 RU RU2019116174A patent/RU2766586C2/ru active
- 2017-10-27 US US16/344,689 patent/US20200054762A1/en active Pending
- 2017-10-27 WO PCT/JP2017/038986 patent/WO2018079740A1/ja active Application Filing
- 2017-10-27 JP JP2017563359A patent/JP7206590B2/ja active Active
- 2017-10-27 BR BR112019008335A patent/BR112019008335A2/pt unknown
- 2017-10-27 AU AU2017348734A patent/AU2017348734A1/en active Pending
- 2017-10-27 CN CN201780066545.4A patent/CN109890417A/zh active Pending
- 2017-10-27 MX MX2019004779A patent/MX2019004779A/es unknown
- 2017-10-27 CA CA3041979A patent/CA3041979A1/en active Pending
-
2023
- 2023-01-04 JP JP2023000134A patent/JP2023026581A/ja active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010016525A1 (ja) * | 2008-08-05 | 2010-02-11 | 東レ株式会社 | 免疫誘導剤 |
WO2010095463A1 (ja) * | 2009-02-20 | 2010-08-26 | 有限会社メイショウ | 免疫増強組成物及びそれを製造する方法 |
WO2013147169A1 (ja) * | 2012-03-30 | 2013-10-03 | 東レ株式会社 | 肝臓癌の治療及び/又は予防用医薬組成物 |
JP2015524399A (ja) * | 2012-07-18 | 2015-08-24 | シャンハイ バーディー バイオテック インコーポレイテッド | 標的免疫療法のための化合物 |
JP2016516798A (ja) * | 2013-04-22 | 2016-06-09 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ヒトのcsf−1rに対する抗体及びtlr9アゴニストの併用療法 |
WO2015020212A1 (ja) * | 2013-08-09 | 2015-02-12 | 東レ株式会社 | 癌の治療及び/又は予防用医薬組成物 |
Non-Patent Citations (1)
Title |
---|
CHEADLE E.ET AL.: "A TLR7 agonist enhances the anti-tumour efficacy of obinutuzumab through an NK cell/CD4 dependent me", EUROPEAN JOURNAL OF CANCER, vol. Vol.61,suppl.1, JPN6018001578, July 2016 (2016-07-01), pages 211 - 910, ISSN: 0004880850 * |
Also Published As
Publication number | Publication date |
---|---|
KR20240005247A (ko) | 2024-01-11 |
US20200054762A1 (en) | 2020-02-20 |
CA3041979A1 (en) | 2018-05-03 |
EP3533466A4 (en) | 2020-06-10 |
RU2019116174A3 (ja) | 2021-02-20 |
KR20190075921A (ko) | 2019-07-01 |
AU2017348734A1 (en) | 2019-05-16 |
JP7206590B2 (ja) | 2023-01-18 |
RU2019116174A (ru) | 2020-11-30 |
BR112019008335A2 (pt) | 2020-01-28 |
EP3533466A1 (en) | 2019-09-04 |
JP2023026581A (ja) | 2023-02-24 |
CN109890417A (zh) | 2019-06-14 |
RU2766586C2 (ru) | 2022-03-15 |
WO2018079740A1 (ja) | 2018-05-03 |
MX2019004779A (es) | 2019-08-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7206590B2 (ja) | 癌の治療及び/又は予防用医薬組成物 | |
JP7342701B2 (ja) | 癌の治療及び/又は予防用医薬組成物 | |
US20220057402A1 (en) | Glycan-Interacting Compounds and Methods of Use | |
ES2909746T3 (es) | Dosificaciones de inmunoconjugados de anticuerpos y SN-38 para una eficacia mejorada y una toxicidad disminuida | |
BR112019018043A2 (pt) | método de tratamento de câncer, e, conjugado de anticorpo-fármaco | |
BR112020005212A2 (pt) | conjugado de anticorpo, kit, composição farmacêutica, e, métodos de tratamento ou prevenção e de diagnóstico de uma doença ou condição. | |
JP2023089195A (ja) | グリピカン3抗体およびそのコンジュゲート | |
KR20200044044A (ko) | 항체-약물 콘주게이트의 제제 및 그 동결 건조 방법 | |
AU2022259796A1 (en) | Antibody drug conjugates comprising STING agonists | |
KR20210042120A (ko) | 항체-약물 콘주게이트와 튜불린 저해제의 조합 | |
US20160264684A1 (en) | Glycan-interacting compounds and methods of use | |
JP2022500413A (ja) | Toll様受容体アゴニストの抗体コンジュゲート | |
CN113646008A (zh) | pHLIP®肽介导的细胞表面的表位束缚 | |
CN113271942A (zh) | 抗体-药物缀合物与parp抑制剂的组合 | |
JP2023504286A (ja) | 薬物送達のためのデンドリマー組成物および方法 | |
TW201739472A (zh) | 抗磷脂醯肌醇蛋白聚糖-3抗體及妥布賴森(tubulysin)類似物之抗體藥物結合物、製備及用途 | |
CN111087465B (zh) | 一种针对密蛋白6的抗体偶联药物及应用 | |
US20230346969A1 (en) | Intermediate for preparing antibody-drug conjugate (adc), preparation method therefor, and use thereof | |
TW202210519A (zh) | 抗c-Met抗體藥物偶聯物及其應用 | |
ES2747836T3 (es) | Métodos y productos para prevenir y/o tratar el cáncer metastásico | |
WO2023033129A1 (ja) | 癌の治療及び/又は予防用医薬組成物 | |
WO2024005123A1 (ja) | 癌の治療及び/又は予防用医薬組成物 | |
WO2019045025A1 (ja) | ワクチン組成物 | |
WO2023190827A1 (ja) | pH依存性抗硫酸化グリコサミノグリカン抗体及び抗体薬物複合体 | |
JP2022535816A (ja) | コラーゲン結合薬物担体を用いてがんを処置するための方法および組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20190205 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201026 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201026 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20211012 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211213 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220420 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220615 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220927 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221121 |
|
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: 20221206 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20221219 |
|
R151 | Written notification of patent or utility model registration |
Ref document number: 7206590 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R151 |