JP2020506176A5 - - Google Patents

Info

Publication number

JP2020506176A5

JP2020506176A5 JP2019539200A JP2019539200A JP2020506176A5 JP 2020506176 A5 JP2020506176 A5 JP 2020506176A5 JP 2019539200 A JP2019539200 A JP 2019539200A JP 2019539200 A JP2019539200 A JP 2019539200A JP 2020506176 A5 JP2020506176 A5 JP 2020506176A5

Authority

JP

Japan

Prior art keywords

adc

antibody

amatoxin

adc according

chain variable

Prior art date

2018-01-19

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

• Espacenet
• Global Dossier
• Discuss

• 239000000611 antibody drug conjugate Substances 0.000 claims 27
• 229940049595 antibody-drug conjugate Drugs 0.000 claims 27
• WVHGJJRMKGDTEC-WCIJHFMNSA-N 2-[(1R,4S,8R,10S,13S,16S,27R,34S)-34-[(2S)-butan-2-yl]-8,22-dihydroxy-13-[(2R,3S)-3-hydroxybutan-2-yl]-2,5,11,14,27,30,33,36,39-nonaoxo-27lambda4-thia-3,6,12,15,25,29,32,35,38-nonazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19(24),20,22-tetraen-4-yl]acetamide Chemical compound CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@@H]2Cc3c([nH]c4cc(O)ccc34)[S@](=O)C[C@H](NC(=O)CNC1=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H]([C@@H](C)[C@H](C)O)C(=O)N2 WVHGJJRMKGDTEC-WCIJHFMNSA-N 0.000 claims 14
• 231100000729 Amatoxin Toxicity 0.000 claims 13
• 108010014709 amatoxin Proteins 0.000 claims 13
• 231100000599 cytotoxic agent Toxicity 0.000 claims 9
• 239000002619 cytotoxin Substances 0.000 claims 9
• 125000001424 substituent group Chemical group 0.000 claims 9
• 208000009329 Graft vs Host Disease Diseases 0.000 claims 7
• 208000024908 graft versus host disease Diseases 0.000 claims 7
• 101710112752 Cytotoxin Proteins 0.000 claims 6
• 239000000539 dimer Substances 0.000 claims 6
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims 6
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims 5
• 125000003275 alpha amino acid group Chemical group 0.000 claims 4
• 125000005647 linker group Chemical group 0.000 claims 4
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 3
• 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims 3
• FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
• 108010016626 Dipeptides Proteins 0.000 claims 3
• 108010053187 Diphtheria Toxin Proteins 0.000 claims 3
• 102000016607 Diphtheria Toxin Human genes 0.000 claims 3
• 102000029749 Microtubule Human genes 0.000 claims 3
• 108091022875 Microtubule Proteins 0.000 claims 3
• 108700033844 Pseudomonas aeruginosa toxA Proteins 0.000 claims 3
• 108010084592 Saporins Proteins 0.000 claims 3
• 150000001345 alkine derivatives Chemical class 0.000 claims 3
• 125000000217 alkyl group Chemical group 0.000 claims 3
• 125000004419 alkynylene group Chemical group 0.000 claims 3
• 229940045799 anthracyclines and related substance Drugs 0.000 claims 3
• 125000003118 aryl group Chemical group 0.000 claims 3
• 125000000732 arylene group Chemical group 0.000 claims 3
• 108010044540 auristatin Proteins 0.000 claims 3
• 239000011230 binding agent Substances 0.000 claims 3
• 238000005859 coupling reaction Methods 0.000 claims 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims 3
• 125000002993 cycloalkylene group Chemical group 0.000 claims 3
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 3
• -1 debowganin Proteins 0.000 claims 3
• 229960005501 duocarmycin Drugs 0.000 claims 3
• VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 claims 3
• 229930184221 duocarmycin Natural products 0.000 claims 3
• 210000003958 hematopoietic stem cell Anatomy 0.000 claims 3
• 125000004474 heteroalkylene group Chemical group 0.000 claims 3
• 125000001072 heteroaryl group Chemical group 0.000 claims 3
• 125000005549 heteroarylene group Chemical group 0.000 claims 3
• 125000006588 heterocycloalkylene group Chemical group 0.000 claims 3
• 102000050327 human TNFRSF9 Human genes 0.000 claims 3
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 3
• 229960004768 irinotecan Drugs 0.000 claims 3
• 210000004688 microtubule Anatomy 0.000 claims 3
• 125000004430 oxygen atom Chemical group O* 0.000 claims 3
• 239000000126 substance Substances 0.000 claims 3
• 101800002638 Alpha-amanitin Proteins 0.000 claims 2
• 108010027164 Amanitins Proteins 0.000 claims 2
• 210000001744 T-lymphocyte Anatomy 0.000 claims 2
• CIORWBWIBBPXCG-JZTFPUPKSA-N amanitin Chemical compound O=C1N[C@@H](CC(N)=O)C(=O)N2CC(O)C[C@H]2C(=O)N[C@@H](C(C)[C@@H](O)CO)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H](C(C)CC)C(=O)NCC(=O)N[C@H]1CS(=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-JZTFPUPKSA-N 0.000 claims 2
• BOHCOUQZNDPURZ-ICNZIKDASA-N 2-[(1R,4S,8R,10S,13S,16S,27R,34S)-34-[(2S)-butan-2-yl]-13-[(2R,3R)-3,4-dihydroxybutan-2-yl]-8-hydroxy-2,5,11,14,27,30,33,36,39-nonaoxo-27lambda4-thia-3,6,12,15,25,29,32,35,38-nonazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19,21,23-tetraen-4-yl]acetamide Chemical compound CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@@H]2Cc3c([nH]c4ccccc34)[S@](=O)C[C@H](NC(=O)CNC1=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H]([C@@H](C)[C@@H](O)CO)C(=O)N2 BOHCOUQZNDPURZ-ICNZIKDASA-N 0.000 claims 1
• QCZXQEYEVLCQHL-UHFFFAOYSA-N Amanin Natural products O=C1NC(CC(O)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(O)CO)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=CC=C2N1 QCZXQEYEVLCQHL-UHFFFAOYSA-N 0.000 claims 1
• 101800001350 Beta-amanitin Proteins 0.000 claims 1
• RXGJTYFDKOHJHK-UHFFFAOYSA-N S-deoxo-amaninamide Natural products CCC(C)C1NC(=O)CNC(=O)C2Cc3c(SCC(NC(=O)CNC1=O)C(=O)NC(CC(=O)N)C(=O)N4CC(O)CC4C(=O)NC(C(C)C(O)CO)C(=O)N2)[nH]c5ccccc35 RXGJTYFDKOHJHK-UHFFFAOYSA-N 0.000 claims 1
• 238000011316 allogeneic transplantation Methods 0.000 claims 1
• 239000004007 alpha amanitin Substances 0.000 claims 1
• CIORWBWIBBPXCG-SXZCQOKQSA-N alpha-amanitin Chemical compound O=C1N[C@@H](CC(N)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)[C@@H](O)CO)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1C[S@@](=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-SXZCQOKQSA-N 0.000 claims 1
• CIORWBWIBBPXCG-UHFFFAOYSA-N alpha-amanitin Natural products O=C1NC(CC(N)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(O)CO)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-UHFFFAOYSA-N 0.000 claims 1
• QCZXQEYEVLCQHL-MIBTZWEZSA-N amanin Chemical compound O=C1N[C@@H](CC(O)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)[C@@H](O)CO)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1CS(=O)C1=C2C2=CC=CC=C2N1 QCZXQEYEVLCQHL-MIBTZWEZSA-N 0.000 claims 1
• 108010004258 amaninamide Proteins 0.000 claims 1
• BOHCOUQZNDPURZ-UHFFFAOYSA-N amaninamide Natural products O=C1NC(CC(N)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(O)CO)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=CC=C2N1 BOHCOUQZNDPURZ-UHFFFAOYSA-N 0.000 claims 1
• QQLVIKWYAVVKKF-XYDKGUIVSA-N amanullin Chemical compound O=C1N[C@@H](CC(N)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1CS(=O)C1=C2C2=CC=C(O)C=C2N1 QQLVIKWYAVVKKF-XYDKGUIVSA-N 0.000 claims 1
• HFENEIQMWRYNGK-XYDKGUIVSA-N amanullinic acid Chemical compound O=C1N[C@@H](CC(O)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1CS(=O)C1=C2C2=CC=C(O)C=C2N1 HFENEIQMWRYNGK-XYDKGUIVSA-N 0.000 claims 1
• 239000004080 beta amanitin Substances 0.000 claims 1
• IEQCUEXVAPAFMQ-UHFFFAOYSA-N beta-amanitin Natural products O=C1NC(CC(O)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(O)CO)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=C(O)C=C2N1 IEQCUEXVAPAFMQ-UHFFFAOYSA-N 0.000 claims 1
• 210000001185 bone marrow Anatomy 0.000 claims 1
• 210000004027 cell Anatomy 0.000 claims 1
• 230000000779 depleting effect Effects 0.000 claims 1
• 210000004700 fetal blood Anatomy 0.000 claims 1
• IEQCUEXVAPAFMQ-SXZCQOKQSA-N g729ypp47l Chemical compound O=C1N[C@@H](CC(O)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)[C@@H](O)CO)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1C[S@@](=O)C1=C2C2=CC=C(O)C=C2N1 IEQCUEXVAPAFMQ-SXZCQOKQSA-N 0.000 claims 1
• WVHGJJRMKGDTEC-UHFFFAOYSA-N gamma-amanitin Natural products O=C1NC(CC(N)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(C)O)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=C(O)C=C2N1 WVHGJJRMKGDTEC-UHFFFAOYSA-N 0.000 claims 1
• 210000005259 peripheral blood Anatomy 0.000 claims 1
• 239000011886 peripheral blood Substances 0.000 claims 1
• CTYHFRWAIRSHQT-YRDOMICZSA-N proamanullin Chemical compound O=C1N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1CS(=O)C1=C2C2=CC=C(O)C=C2N1 CTYHFRWAIRSHQT-YRDOMICZSA-N 0.000 claims 1
• 229960005502 α-amanitin Drugs 0.000 claims 1
• OFILNAORONITPV-ZUROAWGWSA-N ε-amanitin Chemical compound O=C1N[C@@H](CC(O)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)[C@H](C)O)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1CS(=O)C1=C2C2=CC=C(O)C=C2N1 OFILNAORONITPV-ZUROAWGWSA-N 0.000 claims 1
• 0 C*[N+](*C(C(CC(C(C)(C)I)=C(*CC*[C@@](C)O)*(C)=C)*C=O)O)[O-] Chemical compound C*[N+](*C(C(CC(C(C)(C)I)=C(*CC*[C@@](C)O)*(C)=C)*C=O)O)[O-] 0.000 description 1