JPWO2020081841A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2020081841A5 JPWO2020081841A5 JP2021521098A JP2021521098A JPWO2020081841A5 JP WO2020081841 A5 JPWO2020081841 A5 JP WO2020081841A5 JP 2021521098 A JP2021521098 A JP 2021521098A JP 2021521098 A JP2021521098 A JP 2021521098A JP WO2020081841 A5 JPWO2020081841 A5 JP WO2020081841A5
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- compound
- domain
- pharmaceutical composition
- antibody
- 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
- 150000001875 compounds Chemical class 0.000 claims description 45
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 201000011510 cancer Diseases 0.000 claims description 14
- 239000012634 fragment Substances 0.000 claims description 14
- 230000008685 targeting Effects 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 9
- 108010024976 Asparaginase Proteins 0.000 claims description 6
- 102100026094 C-type lectin domain family 12 member A Human genes 0.000 claims description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 6
- 101000912622 Homo sapiens C-type lectin domain family 12 member A Proteins 0.000 claims description 6
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 6
- 206010038389 Renal cancer Diseases 0.000 claims description 6
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 6
- 201000005787 hematologic cancer Diseases 0.000 claims description 6
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 6
- 201000010982 kidney cancer Diseases 0.000 claims description 6
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 4
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 4
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- 210000000822 natural killer cell Anatomy 0.000 claims description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 3
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 claims description 3
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 3
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims description 3
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 3
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
- 102000015790 Asparaginase Human genes 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 108010006654 Bleomycin Proteins 0.000 claims description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 3
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 3
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 3
- 108010092160 Dactinomycin Proteins 0.000 claims description 3
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 3
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 3
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 3
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 3
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 3
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 3
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 3
- 229960000473 altretamine Drugs 0.000 claims description 3
- 229960001220 amsacrine Drugs 0.000 claims description 3
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims description 3
- 229960001561 bleomycin Drugs 0.000 claims description 3
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 3
- 229960002092 busulfan Drugs 0.000 claims description 3
- 229960004117 capecitabine Drugs 0.000 claims description 3
- 229960004562 carboplatin Drugs 0.000 claims description 3
- 190000008236 carboplatin Chemical compound 0.000 claims description 3
- 229960005243 carmustine Drugs 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 3
- 229960004630 chlorambucil Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- 229960002436 cladribine Drugs 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 229960004397 cyclophosphamide Drugs 0.000 claims description 3
- 229960000684 cytarabine Drugs 0.000 claims description 3
- 229960003901 dacarbazine Drugs 0.000 claims description 3
- 229960000640 dactinomycin Drugs 0.000 claims description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
- 229960000975 daunorubicin Drugs 0.000 claims description 3
- 229960003668 docetaxel Drugs 0.000 claims description 3
- 229960004679 doxorubicin Drugs 0.000 claims description 3
- 229960001904 epirubicin Drugs 0.000 claims description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 3
- 229960005420 etoposide Drugs 0.000 claims description 3
- 229960000390 fludarabine Drugs 0.000 claims description 3
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 3
- 229960002949 fluorouracil Drugs 0.000 claims description 3
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 claims description 3
- 229960004783 fotemustine Drugs 0.000 claims description 3
- 229960002963 ganciclovir Drugs 0.000 claims description 3
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 3
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 3
- 229960005277 gemcitabine Drugs 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical group CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 3
- 229960000908 idarubicin Drugs 0.000 claims description 3
- -1 ifosfamaide Chemical compound 0.000 claims description 3
- 229960004768 irinotecan Drugs 0.000 claims description 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 description 3
- 229960002247 lomustine Drugs 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 3
- 229960001924 melphalan Drugs 0.000 claims description 3
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 3
- 229960001428 mercaptopurine Drugs 0.000 claims description 3
- 229960000485 methotrexate Drugs 0.000 claims description 3
- 229960004857 mitomycin Drugs 0.000 claims description 3
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 claims description 3
- 229960001420 nimustine Drugs 0.000 claims description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 3
- 229960001756 oxaliplatin Drugs 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 229960005079 pemetrexed Drugs 0.000 claims description 3
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 3
- 229960000624 procarbazine Drugs 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 229960004432 raltitrexed Drugs 0.000 claims description 3
- 206010038038 rectal cancer Diseases 0.000 claims description 3
- 201000001275 rectum cancer Diseases 0.000 claims description 3
- 238000002271 resection Methods 0.000 claims description 3
- 201000000849 skin cancer Diseases 0.000 claims description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
- 229960004964 temozolomide Drugs 0.000 claims description 3
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 3
- 229960001278 teniposide Drugs 0.000 claims description 3
- 229960001196 thiotepa Drugs 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 229960003087 tioguanine Drugs 0.000 claims description 3
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims description 3
- 229960000303 topotecan Drugs 0.000 claims description 3
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- 229960003048 vinblastine Drugs 0.000 claims description 3
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
- 229960004355 vindesine Drugs 0.000 claims description 3
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 claims description 3
- 229960002066 vinorelbine Drugs 0.000 claims description 3
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 3
- 206010061523 Lip and/or oral cavity cancer Diseases 0.000 claims description 2
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 claims description 2
- 206010034811 Pharyngeal cancer Diseases 0.000 claims description 2
- 210000004899 c-terminal region Anatomy 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 230000001939 inductive effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 13
- 206010043515 Throat cancer Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
Description
いくつかの実施形態では、対象における癌を治療する方法を本明細書に提供し、本方法は、癌を治療するのに有効な量の本明細書に記載の化合物を対象に投与することを含む。いくつかの実施形態では、癌には、前立腺癌、肺癌、結腸癌、直腸癌、膀胱癌、黒色腫、腎臓癌、腎癌、口腔癌、咽頭癌、膵臓癌、子宮癌、甲状腺癌、皮膚癌、頭頸部癌、子宮頸癌、卵巣癌、または造血性癌が含まれる。いくつかの実施形態では、本明細書で提供される方法は、化学療法、腫瘍の外科的切除、または放射線療法の前、同時、または後に化合物を投与することをさらに含む。いくつかの実施形態では、化学療法は、アルトレタミン、アムサクリン、Ｌ－アスパラギナーゼ、コラスパーゼ（ｃｏｌａｓｐａｓｅ）、ブレオマイシン、ブスルファン、カペシタビン、カルボプラチン、カルムスチン、クロランブシル、シスプラチン、クラドリビン、シクロホスファミド、サイトホスファン（ｃｙｔｏｐｈｏｓｐｈａｎｅ）、シタラビン、ダカルバジン、ダクチノマイシン、ダウノルビシン、ドセタキセル、ドキソルビシン、エピルビシン、エトポシド、フルオロウラシル、フルダラビン、フォテムスチン、ガンシクロビル、ゲムシタビン、ヒドロキシ尿素、イダルビシン、イフォスファマイド（ｉｆｏｓｆａｍａｉｄｅ）、イリノテカン、ロムスチン、メルファラン、メルカプトプリン、メトトレキサート、ミトキサントロン、マイトマイシンＣ、ニムスチン、オキサリプラチン、パクリタキセル、ペメトレキセド、プロカルバジン、ラルチトレキセド、テモゾロミド、テニポシド、チオグアニン、チオテパ、トポテカン、ビンブラスチン、ビンクリスチン、ビンデシン、およびビノレルビンを含む。いくつかの実施形態では、造血性癌は、ＡＭＬである。
[本発明1001]
ＮＫ結合ドメインと、
前記ＮＫ結合ドメインに作動可能に連結されたＮＫ活性化ドメインと、
標的細胞に選択的に結合する標的指向ドメインであって、前記ＮＫ活性化ドメインおよび前記ＮＫ結合ドメインに作動可能に連結された、前記標的指向ドメインと
を含む、化合物であって、
前記標的指向ドメインが、ＣＬＥＣ１２Ａに選択的に結合する、
前記化合物。
[本発明1002]
前記ＮＫ結合ドメインが、ＣＤ１６に選択的に結合する部分を含む、本発明1001の化合物。
[本発明1003]
前記ＮＫ結合ドメイン部分が、抗体またはその結合フラグメント、あるいはナノボディを含む、本発明1001の化合物。
[本発明1004]
前記抗体結合フラグメントが、ｓｃＦｖ、Ｆ（ａｂ）２、またはＦａｂを含む、本発明1003の化合物。
[本発明1005]
前記抗体またはその結合フラグメントあるいは前記ナノボディが、ヒトのものであるかまたはヒト化されている、本発明1003の化合物。
[本発明1006]
前記抗体またはその結合フラグメントあるいは前記ナノボディが、ラクダ科動物のものである、本発明1003の化合物。
[本発明1007]
前記ＮＫ活性化ドメインが、ＩＬ－１５またはその機能的フラグメントを含む、本発明1001の化合物。
[本発明1008]
前記ＩＬ－１５が、配列番号９のアミノ酸配列またはその機能的変異体を含む、本発明1007の化合物。
[本発明1009]
前記標的指向ドメイン部分が、抗体またはその結合フラグメント、あるいはナノボディを含む、本発明1001の化合物。
[本発明1010]
前記抗体結合フラグメントが、ｓｃＦｖ、Ｆ（ａｂ）２、またはＦａｂを含む、本発明1009の化合物。
[本発明1011]
前記ＮＫ結合ドメインが、ＣＤ１６に選択的に結合する部分を含み、前記ＮＫ活性化ドメインが、ＩＬ－１５を含み、かつ前記標的指向ドメインが、ＣＬＥＣ１２Ａに選択的に結合する、本発明1001の化合物。
[本発明1012]
前記ドメインのうちの２つを連結する少なくとも１つの隣接配列を含む、本発明1001の化合物。
[本発明1013]
前記２つの連結されたドメインを第３のドメインと連結する第２の隣接配列をさらに含む、本発明1012の化合物。
[本発明1014]
前記隣接配列が、前記ＮＫ活性化ドメインに隣接している、本発明1013の化合物。
[本発明1015]
第１の隣接配列が、前記ＮＫ結合ドメインのＣ末端側であり、かつ第２の隣接配列が、前記抗ＣＬＥＣ１２Ａ標的指向ドメインのＮ末端側である、本発明1014の化合物。
[本発明1016]
配列番号１を含む、単離されたアミノ酸配列。
[本発明1017]
配列番号１のアミノ酸配列をコードする、単離されたＤＮＡ配列。
[本発明1018]
配列番号２を含む、単離されたアミノ酸配列。
[本発明1019]
配列番号２のアミノ酸配列をコードする、単離されたＤＮＡ配列。
[本発明1020]
前記ＣＬＥＣ１２Ａドメインが、配列番号４に記載されている、本発明1001の化合物。
[本発明1021]
本発明1001の化合物と、
薬学的に許容される担体と
を含む、組成物。
[本発明1022]
標的細胞のＮＫ媒介性殺傷を誘導するのに有効な量の本発明1001の化合物を対象に投与することを含む、方法。
[本発明1023]
前記標的細胞が、癌細胞である、本発明1022の方法。
[本発明1024]
インビボでＮＫ細胞の増殖を刺激するための方法であって、
対象におけるＮＫ細胞の増殖を刺激するのに有効な量の本発明1001の化合物を前記対象に投与すること
を含む、前記方法。
[本発明1025]
対象の癌を治療する方法であって、
前記癌を治療するのに有効な量の本発明1001の化合物を前記対象に投与すること
を含む、前記方法。
[本発明1026]
前記癌が、前立腺癌、肺癌、結腸癌、直腸癌、膀胱癌、黒色腫、腎臓癌、腎癌、口腔癌、咽頭癌、膵臓癌、子宮癌、甲状腺癌、皮膚癌、頭頸部癌、子宮頸癌、卵巣癌、または造血性癌を含む、本発明1025の方法。
[本発明1027]
化学療法、腫瘍の外科的切除、または放射線療法の前、同時、または後に前記化合物を投与することをさらに含む、本発明1026の方法。
[本発明1028]
前記化学療法が、アルトレタミン、アムサクリン、Ｌ－アスパラギナーゼ、コラスパーゼ（ｃｏｌａｓｐａｓｅ）、ブレオマイシン、ブスルファン、カペシタビン、カルボプラチン、カルムスチン、クロランブシル、シスプラチン、クラドリビン、シクロホスファミド、サイトホスファン（ｃｙｔｏｐｈｏｓｐｈａｎｅ）、シタラビン、ダカルバジン、ダクチノマイシン、ダウノルビシン、ドセタキセル、ドキソルビシン、エピルビシン、エトポシド、フルオロウラシル、フルダラビン、フォテムスチン、ガンシクロビル、ゲムシタビン、ヒドロキシ尿素、イダルビシン、イフォスファマイド（ｉｆｏｓｆａｍａｉｄｅ）、イリノテカン、ロムスチン、メルファラン、メルカプトプリン、メトトレキサート、ミトキサントロン、マイトマイシンＣ、ニムスチン、オキサリプラチン、パクリタキセル、ペメトレキセド、プロカルバジン、ラルチトレキセド、テモゾロミド、テニポシド、チオグアニン、チオテパ、トポテカン、ビンブラスチン、ビンクリスチン、ビンデシン、およびビノレルビンを含む、本発明1027の方法。
[本発明1029]
前記造血性癌が、ＡＭＬである、本発明1026の方法。
In some embodiments, provided herein are methods of treating cancer in a subject, the methods comprising administering to the subject an amount of a compound described herein effective to treat cancer. include. In some embodiments, cancer includes prostate cancer, lung cancer, colon cancer, rectal cancer, bladder cancer, melanoma, kidney cancer, renal cancer, oral cancer, throat cancer, pancreatic cancer, uterine cancer, thyroid cancer, skin cancer. Included are cancer, head and neck cancer, cervical cancer, ovarian cancer, or hematopoietic cancer. In some embodiments, the methods provided herein further comprise administering a compound prior to, concurrently with, or after chemotherapy, surgical resection of the tumor, or radiation therapy. In some embodiments, the chemotherapy is altretamine, amsacrine, L-asparaginase, colaspase, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytophosphane ), cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fluorouracil, fludarabine, fotemustine, ganciclovir, gemcitabine, hydroxyurea, idarubicin, ifosfamaide, irinotecan, lomustine, melphalan, Mercaptopurine, methotrexate, mitoxantrone, mitomycin C, nimustine, oxaliplatin, paclitaxel, pemetrexed, procarbazine, raltitrexed, temozolomide, teniposide, thioguanine, thiotepa, topotecan, vinblastine, vincristine, vindesine, and vinorelbine. In some embodiments, the hematopoietic cancer is AML.
[Invention 1001]
an NK binding domain;
an NK activation domain operably linked to the NK binding domain;
a targeting domain that selectively binds to a target cell, said targeting domain being operably linked to said NK activation domain and said NK binding domain;
A compound comprising
said targeting domain selectively binds to CLEC12A;
said compound.
[Invention 1002]
1001. The compound of the invention 1001, wherein said NK binding domain comprises a portion that selectively binds to CD16.
[Invention 1003]
1001. The compound of the invention 1001, wherein said NK binding domain portion comprises an antibody or binding fragment thereof, or a Nanobody.
[Invention 1004]
1003. The compound of the invention 1003, wherein said antibody binding fragment comprises scFv, F(ab)2, or Fab.
[Invention 1005]
1003. The compound of the invention 1003, wherein said antibody or binding fragment thereof or said Nanobody is human or humanized.
[Invention 1006]
1003. The compound of the invention 1003, wherein said antibody or binding fragment thereof or said Nanobody is camelid.
[Invention 1007]
1001. The compound of the invention 1001, wherein said NK activation domain comprises IL-15 or a functional fragment thereof.
[Invention 1008]
1007. The compound of the invention 1007, wherein said IL-15 comprises the amino acid sequence of SEQ ID NO:9 or a functional variant thereof.
[Invention 1009]
1001. The compound of the invention 1001, wherein said targeting domain portion comprises an antibody or binding fragment thereof, or a Nanobody.
[Invention 1010]
1009. The compound of the invention 1009, wherein said antibody binding fragment comprises scFv, F(ab)2, or Fab.
[Invention 1011]
1001. The compound of the invention 1001, wherein said NK binding domain comprises a moiety that selectively binds to CD16, said NK activation domain comprises IL-15, and said targeting domain selectively binds to CLEC12A. .
[Invention 1012]
1001. A compound of the invention 1001 comprising at least one flanking sequence linking two of said domains.
[Invention 1013]
1012. The compound of the invention 1012 further comprising a second flanking sequence linking said two linked domains with a third domain.
[Invention 1014]
1013. The compound of the invention 1013, wherein said flanking sequences flank said NK activation domain.
[Invention 1015]
1014. The compound of the invention 1014, wherein a first flanking sequence is C-terminal to said NK binding domain and a second flanking sequence is N-terminal to said anti-CLEC12A targeting domain.
[Invention 1016]
An isolated amino acid sequence, including SEQ ID NO:1.
[Invention 1017]
An isolated DNA sequence encoding the amino acid sequence of SEQ ID NO:1.
[Invention 1018]
An isolated amino acid sequence, including SEQ ID NO:2.
[Invention 1019]
An isolated DNA sequence encoding the amino acid sequence of SEQ ID NO:2.
[Invention 1020]
1001. The compound of the invention 1001, wherein said CLEC12A domain is set forth in SEQ ID NO:4.
[Invention 1021]
a compound of the present invention 1001;
a pharmaceutically acceptable carrier and
A composition comprising:
[Invention 1022]
A method comprising administering to a subject an amount of a compound of invention 1001 effective to induce NK-mediated killing of a target cell.
[Invention 1023]
1023. The method of invention 1022, wherein said target cell is a cancer cell.
[Invention 1024]
A method for stimulating NK cell proliferation in vivo comprising:
administering to said subject an amount of a compound of the present invention 1001 effective to stimulate proliferation of NK cells in said subject
The above method, comprising
[Invention 1025]
A method of treating cancer in a subject, comprising:
administering to said subject an amount of a compound of the invention 1001 effective to treat said cancer
The above method, comprising
[Invention 1026]
The cancer is prostate cancer, lung cancer, colon cancer, rectal cancer, bladder cancer, melanoma, kidney cancer, renal cancer, mouth cancer, pharyngeal cancer, pancreatic cancer, uterine cancer, thyroid cancer, skin cancer, head and neck cancer, child cancer The method of the invention 1025, comprising cervical cancer, ovarian cancer, or hematopoietic cancer.
[Invention 1027]
The method of invention 1026, further comprising administering said compound prior to, concurrently with, or after chemotherapy, surgical resection of the tumor, or radiation therapy.
[Invention 1028]
said chemotherapy is altretamine, amsacrine, L-asparaginase, colaspase, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytophosphane, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fluorouracil, fludarabine, fotemustine, ganciclovir, gemcitabine, hydroxyurea, idarubicin, ifosfamaide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitoki 1027. The method of the present invention, comprising santron, mitomycin C, nimustine, oxaliplatin, paclitaxel, pemetrexed, procarbazine, raltitrexed, temozolomide, teniposide, thioguanine, thiotepa, topotecan, vinblastine, vincristine, vindesine, and vinorelbine.
[Invention 1029]
1026. The method of the invention 1026, wherein said hematopoietic cancer is AML.
Claims (29)
前記ＮＫ結合ドメインに作動可能に連結されたＮＫ活性化ドメインと、
標的細胞に選択的に結合する標的指向ドメインであって、前記ＮＫ活性化ドメインおよび前記ＮＫ結合ドメインに作動可能に連結された、前記標的指向ドメインと
を含む、化合物であって、
前記標的指向ドメインが、ＣＬＥＣ１２Ａに選択的に結合する、
前記化合物。 an NK binding domain;
an NK activation domain operably linked to the NK binding domain;
a targeting domain that selectively binds to a target cell, said targeting domain operably linked to said NK activation domain and said NK binding domain, said compound comprising:
said targeting domain selectively binds to CLEC12A;
said compound.
薬学的に許容される担体と
を含む、組成物。 a compound of claim 1;
and a pharmaceutically acceptable carrier.
対象におけるＮＫ細胞の増殖を刺激するのに有効な量の請求項１に記載の化合物を含む、前記医薬組成物。 A pharmaceutical composition for stimulating NK cell proliferation in a subject , comprising:
11. The pharmaceutical composition comprising an amount of the compound of claim 1 effective to stimulate NK cell proliferation in a subject.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862747983P | 2018-10-19 | 2018-10-19 | |
| US62/747,983 | 2018-10-19 | ||
| PCT/US2019/056777 WO2020081841A1 (en) | 2018-10-19 | 2019-10-17 | Nk engager molecules and methods of use thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022505158A JP2022505158A (en) | 2022-01-14 |
| JPWO2020081841A5 true JPWO2020081841A5 (en) | 2022-10-19 |
| JP7453971B2 JP7453971B2 (en) | 2024-03-21 |
Family
ID=70284811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021521098A Active JP7453971B2 (en) | 2018-10-19 | 2019-10-17 | NK engager molecules and their use |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20210388093A1 (en) |
| EP (1) | EP3867278A4 (en) |
| JP (1) | JP7453971B2 (en) |
| KR (1) | KR20210081346A (en) |
| CN (1) | CN112912400A (en) |
| AU (1) | AU2019361096A1 (en) |
| CA (1) | CA3114707A1 (en) |
| IL (1) | IL282193A (en) |
| WO (1) | WO2020081841A1 (en) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2526284C (en) * | 2003-06-25 | 2014-11-18 | Crucell Holland B.V. | Binding molecules for the treatment of myeloid cell malignancies |
| EP2014680A1 (en) * | 2007-07-10 | 2009-01-14 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Recombinant, single-chain, trivalent tri-specific or bi-specific antibody derivatives |
| DK2900694T3 (en) * | 2012-09-27 | 2018-11-19 | Merus Nv | BISPECIFIC IGG ANTIBODIES AS T-CELL ACTIVATORS |
| US20180021378A1 (en) * | 2014-12-31 | 2018-01-25 | Anthrogenesis Corporation | Methods of treating hematological disorders, solid tumors, or infectious diseases using natural killer cells |
| TW201718647A (en) * | 2015-06-16 | 2017-06-01 | 建南德克公司 | Anti-CLL-1 antibodies and methods of use |
| MX2018004114A (en) * | 2015-10-06 | 2018-08-21 | Univ Minnesota | Therapeutic compounds and methods. |
| ES2847155T3 (en) * | 2016-01-21 | 2021-08-02 | Novartis Ag | Multispecific molecules targeting CLL-1 |
| JP2020534269A (en) * | 2017-09-14 | 2020-11-26 | ドラゴンフライ セラピューティクス， インコーポレイテッド | Protein that binds to NKG2D, CD16, and C-type lectin-like molecule-1 (CLL-1) |
-
2019
- 2019-10-17 JP JP2021521098A patent/JP7453971B2/en active Active
- 2019-10-17 CN CN201980067595.3A patent/CN112912400A/en active Pending
- 2019-10-17 US US17/285,447 patent/US20210388093A1/en active Pending
- 2019-10-17 EP EP19873982.3A patent/EP3867278A4/en active Pending
- 2019-10-17 KR KR1020217011728A patent/KR20210081346A/en unknown
- 2019-10-17 WO PCT/US2019/056777 patent/WO2020081841A1/en unknown
- 2019-10-17 AU AU2019361096A patent/AU2019361096A1/en active Pending
- 2019-10-17 CA CA3114707A patent/CA3114707A1/en active Pending
-
2021
- 2021-04-08 IL IL282193A patent/IL282193A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2018116565A (en) | THERAPEUTIC COMPOUNDS AND METHODS | |
| US9574009B2 (en) | Polynucleotides encoding VEGF/DLL4 binding agents | |
| US20220049001A1 (en) | Anti-met antibodies, bispecific antigen binding molecules that bind met, and methods of use thereof | |
| JP2006500009A5 (en) | ||
| JP2020510653A5 (en) | Multispecific binding protein targeting CEA | |
| CN106573986A (en) | Multispecific antibodies | |
| AU2012314860B2 (en) | Immunocytokine combination therapy | |
| RU2012137503A (en) | DRUG FOR TREATMENT AND / OR PREVENTION OF CANCER | |
| JP4576005B2 (en) | A combination of a substance that causes necrosis and a substance that is activated by necrosis, used to selectively treat tumors and inflammatory diseases | |
| CN111936164A (en) | Pharmaceutical composition for treating and/or preventing cancer | |
| EA021967B1 (en) | Antibody targeting through a modular recognition domain | |
| RU2014141151A (en) | DIAGNOSIS AND TREATMENT OF A MALIGNANT TUMOR USING ANTIBODY AGAINST EREG | |
| JP2010504755A5 (en) | ||
| JP2018510881A5 (en) | ||
| HRP20150256T1 (en) | Notch1 receptor binding agents and methods of use thereof | |
| EP1218032A1 (en) | Treatment of refractory human tumors with epidermal growth factor receptor antagonists | |
| JP2010535713A5 (en) | ||
| JP6447887B2 (en) | Bispecific antibodies and uses thereof | |
| US20200095339A1 (en) | Novel recombinant bi-functional fusion protein, preparation method therefor and use thereof | |
| SI2342234T1 (en) | Monoclonal anti-gt468 antibodies for treatment of cancer | |
| CN102250245A (en) | Bispecific antibody capable of resisting B cell lymphoma and application thereof | |
| US20030202973A1 (en) | Treatment of refractory human tumors with epidermal growth factor receptor and HER1 mitogenic ligand (EGFRML) antagonists | |
| RU2021130306A (en) | IL-12 COMPOSITIONS AIMED AT EDB | |
| CN106810610A (en) | Anti-EpCAM and the double targeting antibodies of CD3 specificity and its preparation method and application, the minicircle dna containing this pair of targeting antibodies expression cassette and application | |
| Kouhsari et al. | The potential roles of bacteria to improve radiation treatment outcome |