JP6865585B2 - 成長分化因子１５（ｇｄｆ−１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 - Google Patents
成長分化因子１５（ｇｄｆ−１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 Download PDFInfo
- Publication number
- JP6865585B2 JP6865585B2 JP2016559286A JP2016559286A JP6865585B2 JP 6865585 B2 JP6865585 B2 JP 6865585B2 JP 2016559286 A JP2016559286 A JP 2016559286A JP 2016559286 A JP2016559286 A JP 2016559286A JP 6865585 B2 JP6865585 B2 JP 6865585B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- amino acid
- seq
- acid sequence
- antigen
- 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.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 215
- 201000011510 cancer Diseases 0.000 title claims description 162
- 206010006895 Cachexia Diseases 0.000 title claims description 142
- 108010041834 Growth Differentiation Factor 15 Proteins 0.000 title claims description 132
- 102000000597 Growth Differentiation Factor 15 Human genes 0.000 title claims description 130
- 230000027455 binding Effects 0.000 claims description 337
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 309
- 239000000427 antigen Substances 0.000 claims description 264
- 102000036639 antigens Human genes 0.000 claims description 264
- 108091007433 antigens Proteins 0.000 claims description 264
- 238000000034 method Methods 0.000 claims description 159
- 101000893549 Homo sapiens Growth/differentiation factor 15 Proteins 0.000 claims description 140
- 102000046181 human GDF15 Human genes 0.000 claims description 140
- 238000011282 treatment Methods 0.000 claims description 59
- 241000124008 Mammalia Species 0.000 claims description 49
- 239000002773 nucleotide Substances 0.000 claims description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 8
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical group OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 7
- 210000004027 cell Anatomy 0.000 description 90
- 208000016261 weight loss Diseases 0.000 description 51
- 230000004580 weight loss Effects 0.000 description 50
- 108090000765 processed proteins & peptides Proteins 0.000 description 48
- 150000001413 amino acids Chemical class 0.000 description 47
- 239000008194 pharmaceutical composition Substances 0.000 description 42
- 230000005907 cancer growth Effects 0.000 description 38
- 230000000694 effects Effects 0.000 description 35
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 33
- 241000699666 Mus <mouse, genus> Species 0.000 description 27
- 108090000623 proteins and genes Proteins 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 23
- 239000003814 drug Substances 0.000 description 20
- 241000699670 Mus sp. Species 0.000 description 19
- 230000005764 inhibitory process Effects 0.000 description 19
- 230000037396 body weight Effects 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 18
- 229940079593 drug Drugs 0.000 description 17
- 238000004113 cell culture Methods 0.000 description 16
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 16
- 238000005259 measurement Methods 0.000 description 16
- 239000000872 buffer Substances 0.000 description 15
- 239000002953 phosphate buffered saline Substances 0.000 description 15
- 201000001441 melanoma Diseases 0.000 description 14
- 238000010494 dissociation reaction Methods 0.000 description 13
- 230000005593 dissociations Effects 0.000 description 13
- 230000000813 microbial effect Effects 0.000 description 12
- 239000002246 antineoplastic agent Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000002265 prevention Effects 0.000 description 11
- 238000010186 staining Methods 0.000 description 11
- 210000002865 immune cell Anatomy 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 206010006187 Breast cancer Diseases 0.000 description 9
- 208000026310 Breast neoplasm Diseases 0.000 description 9
- 206010060862 Prostate cancer Diseases 0.000 description 9
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 9
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 210000000822 natural killer cell Anatomy 0.000 description 9
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 9
- 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 8
- 206010018338 Glioma Diseases 0.000 description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 208000032612 Glial tumor Diseases 0.000 description 7
- -1 PDGF Proteins 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 210000004408 hybridoma Anatomy 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 229960004528 vincristine Drugs 0.000 description 7
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 7
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 7
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 206010033128 Ovarian cancer Diseases 0.000 description 6
- 208000005718 Stomach Neoplasms Diseases 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000013068 control sample Substances 0.000 description 6
- 206010017758 gastric cancer Diseases 0.000 description 6
- 230000001900 immune effect Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 229960004768 irinotecan Drugs 0.000 description 6
- 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 description 6
- 238000004949 mass spectrometry Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 201000011549 stomach cancer Diseases 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 229960000303 topotecan Drugs 0.000 description 6
- 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 description 6
- 208000003174 Brain Neoplasms Diseases 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 241000238631 Hexapoda Species 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 230000004520 agglutination Effects 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000008499 blood brain barrier function Effects 0.000 description 5
- 210000001218 blood-brain barrier Anatomy 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 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 description 4
- 206010005003 Bladder cancer Diseases 0.000 description 4
- 108010006654 Bleomycin Proteins 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 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 description 4
- 101710154606 Hemagglutinin Proteins 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 229930192392 Mitomycin Natural products 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 4
- 238000011794 NU/NU nude mouse Methods 0.000 description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 4
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 4
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 101710176177 Protein A56 Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 4
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 4
- 229930013930 alkaloid Natural products 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 230000000340 anti-metabolite Effects 0.000 description 4
- 229940100197 antimetabolite Drugs 0.000 description 4
- 239000002256 antimetabolite Substances 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 229960001561 bleomycin Drugs 0.000 description 4
- 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 description 4
- 229960004562 carboplatin Drugs 0.000 description 4
- 190000008236 carboplatin Chemical compound 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 229960004316 cisplatin Drugs 0.000 description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 4
- 229960004397 cyclophosphamide Drugs 0.000 description 4
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 4
- 229960003668 docetaxel Drugs 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 229960001904 epirubicin Drugs 0.000 description 4
- 201000004101 esophageal cancer Diseases 0.000 description 4
- 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 description 4
- 229960005420 etoposide Drugs 0.000 description 4
- 239000000185 hemagglutinin Substances 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 229960004857 mitomycin Drugs 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 229960001756 oxaliplatin Drugs 0.000 description 4
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- 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 description 4
- 229960001278 teniposide Drugs 0.000 description 4
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 4
- 229960000575 trastuzumab Drugs 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 201000005112 urinary bladder cancer Diseases 0.000 description 4
- 229960003048 vinblastine Drugs 0.000 description 4
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 4
- 241000283707 Capra Species 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 108010092160 Dactinomycin Proteins 0.000 description 3
- 238000009007 Diagnostic Kit Methods 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 108010087819 Fc receptors Proteins 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- 208000017604 Hodgkin disease Diseases 0.000 description 3
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
- 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- 206010023825 Laryngeal cancer Diseases 0.000 description 3
- 206010062038 Lip neoplasm Diseases 0.000 description 3
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 3
- 208000003445 Mouth Neoplasms Diseases 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 3
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- 229940123237 Taxane Drugs 0.000 description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 description 3
- 206010057644 Testis cancer Diseases 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 229930183665 actinomycin Natural products 0.000 description 3
- 229940045799 anthracyclines and related substance Drugs 0.000 description 3
- 239000003972 antineoplastic antibiotic Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 210000000941 bile Anatomy 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000000112 colonic effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 206010023841 laryngeal neoplasm Diseases 0.000 description 3
- 201000004962 larynx cancer Diseases 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 3
- 201000006721 lip cancer Diseases 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 3
- 229960001428 mercaptopurine Drugs 0.000 description 3
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 201000008006 pharynx cancer Diseases 0.000 description 3
- 229960003171 plicamycin Drugs 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 206010038038 rectal cancer Diseases 0.000 description 3
- 201000001275 rectum cancer Diseases 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010897 surface acoustic wave method Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 201000003120 testicular cancer Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- 101100279186 Caenorhabditis elegans efn-4 gene Proteins 0.000 description 2
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 101000960969 Homo sapiens Interleukin-5 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 2
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101000893547 Mus musculus Growth/differentiation factor 15 Proteins 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000037063 Thinness Diseases 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000009824 affinity maturation Effects 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000002942 anti-growth Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229940127093 camptothecin Drugs 0.000 description 2
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 2
- 230000004611 cancer cell death Effects 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000000235 effect on cancer Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000003966 growth inhibitor Substances 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000017066 negative regulation of growth Effects 0.000 description 2
- 201000011682 nervous system cancer Diseases 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 230000001151 other effect Effects 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 239000000439 tumor marker Substances 0.000 description 2
- 206010048828 underweight Diseases 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 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 description 2
- 229960002066 vinorelbine Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical group CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical class NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 102100038078 CD276 antigen Human genes 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 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 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 101000884279 Homo sapiens CD276 antigen Proteins 0.000 description 1
- 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 description 1
- 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 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054738 Immunologic Receptors Proteins 0.000 description 1
- 102000001749 Immunologic Receptors Human genes 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 102000000812 NK Cell Lectin-Like Receptor Subfamily K Human genes 0.000 description 1
- 108010001657 NK Cell Lectin-Like Receptor Subfamily K Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000002869 basic local alignment search tool Methods 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000020287 immunological synapse formation Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 102220028358 rs386352325 Human genes 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 239000011780 sodium chloride Substances 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
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Cosmetics (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021064572A JP7607498B2 (ja) | 2014-03-26 | 2021-04-06 | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1405477.9A GB2524553C (en) | 2014-03-26 | 2014-03-26 | Monoclonal antibodies to growth and differentiation factor 15 (GDF-15), and uses thereof for treating cancer cachexia |
| GB1405475.3A GB2524552B (en) | 2014-03-26 | 2014-03-26 | Monoclonal antibodies to growth and differentiation factor 15 (GDF-15), and use thereof for treating cancer |
| GB1405475.3 | 2014-03-26 | ||
| GB1405477.9 | 2014-03-26 | ||
| PCT/EP2015/056654 WO2015144855A1 (en) | 2014-03-26 | 2015-03-26 | Monoclonal antibodies to growth and differentiation factor 15 (gdf-15), and uses thereof for treating cancer cachexia and cancer |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021064572A Division JP7607498B2 (ja) | 2014-03-26 | 2021-04-06 | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017508475A JP2017508475A (ja) | 2017-03-30 |
| JP2017508475A5 JP2017508475A5 (enExample) | 2018-05-17 |
| JP6865585B2 true JP6865585B2 (ja) | 2021-04-28 |
Family
ID=52745885
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016559286A Active JP6865585B2 (ja) | 2014-03-26 | 2015-03-26 | 成長分化因子１５（ｇｄｆ−１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
| JP2021064572A Active JP7607498B2 (ja) | 2014-03-26 | 2021-04-06 | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
| JP2023062338A Withdrawn JP2023098966A (ja) | 2014-03-26 | 2023-04-06 | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021064572A Active JP7607498B2 (ja) | 2014-03-26 | 2021-04-06 | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
| JP2023062338A Withdrawn JP2023098966A (ja) | 2014-03-26 | 2023-04-06 | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 |
Country Status (23)
| Country | Link |
|---|---|
| US (5) | US20170204174A1 (enExample) |
| EP (3) | EP3122775B1 (enExample) |
| JP (3) | JP6865585B2 (enExample) |
| KR (1) | KR102520978B1 (enExample) |
| CN (1) | CN106536553B (enExample) |
| AU (2) | AU2015238264B2 (enExample) |
| BR (1) | BR122023027559A2 (enExample) |
| CA (1) | CA2943694A1 (enExample) |
| CY (1) | CY1122456T1 (enExample) |
| DK (2) | DK3122775T3 (enExample) |
| ES (2) | ES2763859T3 (enExample) |
| FI (1) | FI3653644T3 (enExample) |
| HR (2) | HRP20231514T1 (enExample) |
| HU (2) | HUE047398T2 (enExample) |
| IL (2) | IL248038B (enExample) |
| LT (2) | LT3122775T (enExample) |
| NZ (1) | NZ724649A (enExample) |
| PL (2) | PL3122775T3 (enExample) |
| PT (2) | PT3653644T (enExample) |
| RS (1) | RS59700B1 (enExample) |
| SI (1) | SI3122775T1 (enExample) |
| SM (1) | SMT202000064T1 (enExample) |
| WO (1) | WO2015144855A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3122775T3 (da) | 2014-03-26 | 2020-02-03 | Univ Wuerzburg J Maximilians | Monoklonale antistoffer til vækst- og differentieringsfaktor 15 (gdf-15), og anvendelser deraf til behandling af cancer kakeksi og cancer |
| EP3197493B1 (en) | 2014-09-25 | 2021-03-10 | Aveo Pharmaceuticals Inc. | Methods of reversing cachexia and prolonging survival comprising administering a gdf15 modulator and an anti-cancer agent |
| AU2016333538B2 (en) * | 2015-10-02 | 2022-03-31 | Julius-Maximilians-Universität Würzburg | GDF-15 as a diagnostic marker to predict the clinical outcome of a treatment with immune checkpoint blockers |
| GB201517528D0 (en) * | 2015-10-02 | 2015-11-18 | Julius Maximillians Universitãt Würzburg | GDF-15 as a diagnosis marker for melanoma |
| BR112018006218A2 (pt) | 2015-10-02 | 2018-10-09 | Univ Wuerzburg J Maximilians | iinibidores de hgdf-15, seus usos, composição, kit, combinações e método in vitro para determinar se uma substância de interesse é um inibidor de hgdf-15 |
| JP7138567B2 (ja) * | 2016-04-27 | 2022-09-16 | ノバルティス アーゲー | 成長分化因子１５に対する抗体およびそれらの使用 |
| MX389765B (es) * | 2016-07-06 | 2025-03-20 | Nat Res Council Canada | Anticuerpos humanizados que transmigran a traves de la barrera hematoencefalica y usos de los mismos. |
| JP2020503842A (ja) * | 2016-10-12 | 2020-02-06 | ヤンセン バイオテツク，インコーポレーテツド | Ｇｄｆ１５様生物活性の調節因子をスクリーニングするための方法 |
| CA3045700A1 (en) * | 2016-12-06 | 2018-06-14 | St Vincent's Hospital Sydney Limited | Treatment of obesity and eating disorders |
| KR102715542B1 (ko) * | 2018-08-20 | 2024-10-08 | 화이자 인코포레이티드 | 항-gdf15 항체, 조성물 및 사용 방법 |
| AU2021376864A1 (en) * | 2020-11-10 | 2023-06-29 | Catalym Gmbh | Anti-gdf15 antibody and a dosage regimen for the treatment of cancer |
| BR112023020152A2 (pt) | 2021-03-31 | 2023-11-14 | Cambridge Entpr Ltd | Inibidores terapêuticos de sinalização gdf15 |
| US20250019427A1 (en) | 2021-08-10 | 2025-01-16 | Byomass Inc. | Anti-gdf15 antibodies, compositions and uses thereof |
| WO2023122213A1 (en) | 2021-12-22 | 2023-06-29 | Byomass Inc. | Targeting gdf15-gfral pathway cross-reference to related applications |
| WO2023217068A1 (zh) | 2022-05-09 | 2023-11-16 | 舒泰神（北京）生物制药股份有限公司 | 特异性识别gdf15的抗体及其应用 |
| CN116462757A (zh) * | 2023-03-24 | 2023-07-21 | 科兴生物制药股份有限公司 | Gdf15的单域抗体及其应用 |
| CN118878677A (zh) * | 2024-09-29 | 2024-11-01 | 江苏凯基生物技术股份有限公司 | 一种IgM亚型单克隆抗体及其制备方法和应用 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6455677B1 (en) * | 1998-04-30 | 2002-09-24 | Boehringer Ingelheim International Gmbh | FAPα-specific antibody with improved producibility |
| EP0953639A1 (en) * | 1998-04-30 | 1999-11-03 | Boehringer Ingelheim International GmbH | FAPalpha-specific antibody with improved producibility |
| US6465181B2 (en) | 1999-03-25 | 2002-10-15 | Abbott Laboratories | Reagents and methods useful for detecting diseases of the prostate |
| DE60032355T2 (de) | 1999-05-17 | 2007-04-26 | Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Und Zum Vertrieb Von Pharmaka Mbh | NEUROPROTEKTIVE EIGENSCHAFTEN VON GDF-15, EINEM VERTRETER DER TGF-ß-SUPERFAMILIE |
| AU2001288770A1 (en) | 2000-09-08 | 2002-03-22 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | A non-steroidal anti-inflammatory drug activated gene with anti-tumorigenic properties |
| EP3476861A1 (en) * | 2004-01-07 | 2019-05-01 | Novartis Vaccines and Diagnostics, Inc. | M-csf-specific monoclonal antibody and uses thereof |
| ES2555956T3 (es) * | 2004-04-13 | 2016-01-11 | St Vincent's Hospital Sydney Limited | Método para modular el apetito |
| WO2009021293A1 (en) * | 2007-08-16 | 2009-02-19 | St Vincent's Hospital Sydney Limited | Agents and methods for modulating macrophage inhibitory cytokine (mic-1) activity |
| JP2011502106A (ja) * | 2007-10-09 | 2011-01-20 | セントビンセンツ ホスピタル シドニー リミテッド | マクロファージ阻害性サイトカイン−１を除去又は不活性化して悪液質を治療する方法 |
| WO2010034443A1 (en) | 2008-09-29 | 2010-04-01 | F. Hoffmann-La Roche Ag | Antibodies against human il 17 and uses thereof |
| US20120309697A1 (en) | 2009-10-28 | 2012-12-06 | Samuel Norbert Breit | Methods of diagnosing and prognosing colonic polyps |
| US9212221B2 (en) * | 2010-03-03 | 2015-12-15 | Detroit R & D, Inc. | Form-specific antibodies for NAG-1 (MIC-1, GDF-15), H6D and other TGF-β subfamily and heart disease and cancer diagnoses |
| TR201802772T4 (tr) * | 2010-11-17 | 2018-03-21 | Chugai Pharmaceutical Co Ltd | Kan pıhtılaşma faktörü VIII in işlevi için alternatif işleve sahip multi-spesifik antijen bağlayıcı molekül. |
| US8790651B2 (en) | 2011-07-21 | 2014-07-29 | Zoetis Llc | Interleukin-31 monoclonal antibody |
| CN102321173B (zh) | 2011-08-12 | 2013-04-03 | 中国医学科学院肿瘤研究所 | 人源化巨噬细胞抑制因子1单克隆抗体及其应用 |
| EP2565262A1 (en) | 2011-08-31 | 2013-03-06 | VTU Holding GmbH | Protein expression |
| MX2014009129A (es) | 2012-01-26 | 2014-11-21 | Amgen Inc | Polipeptidos de factor 15 de diferenciacion de crecimiento (gdf-15). |
| EP3590537A1 (en) * | 2012-09-26 | 2020-01-08 | Julius-Maximilians-Universität Würzburg | Monoclonal antibodies to growth and differentiation factor 15 (gdf-15) |
| WO2014100689A1 (en) * | 2012-12-21 | 2014-06-26 | Aveo Pharmaceuticals, Inc. | Anti-gdf15 antibodies |
| DK3122775T3 (da) | 2014-03-26 | 2020-02-03 | Univ Wuerzburg J Maximilians | Monoklonale antistoffer til vækst- og differentieringsfaktor 15 (gdf-15), og anvendelser deraf til behandling af cancer kakeksi og cancer |
-
2015
- 2015-03-26 DK DK15712629.3T patent/DK3122775T3/da active
- 2015-03-26 NZ NZ724649A patent/NZ724649A/en unknown
- 2015-03-26 HU HUE15712629A patent/HUE047398T2/hu unknown
- 2015-03-26 SM SM20200064T patent/SMT202000064T1/it unknown
- 2015-03-26 CN CN201580027932.8A patent/CN106536553B/zh active Active
- 2015-03-26 AU AU2015238264A patent/AU2015238264B2/en active Active
- 2015-03-26 PL PL15712629T patent/PL3122775T3/pl unknown
- 2015-03-26 PT PT192053213T patent/PT3653644T/pt unknown
- 2015-03-26 US US15/128,604 patent/US20170204174A1/en not_active Abandoned
- 2015-03-26 FI FIEP19205321.3T patent/FI3653644T3/fi active
- 2015-03-26 HU HUE19205321A patent/HUE064573T2/hu unknown
- 2015-03-26 JP JP2016559286A patent/JP6865585B2/ja active Active
- 2015-03-26 EP EP15712629.3A patent/EP3122775B1/en active Active
- 2015-03-26 HR HRP20231514TT patent/HRP20231514T1/hr unknown
- 2015-03-26 LT LTEP15712629.3T patent/LT3122775T/lt unknown
- 2015-03-26 EP EP23203704.4A patent/EP4316596A3/en active Pending
- 2015-03-26 DK DK19205321.3T patent/DK3653644T5/da active
- 2015-03-26 CA CA2943694A patent/CA2943694A1/en active Pending
- 2015-03-26 HR HRP20200034TT patent/HRP20200034T1/hr unknown
- 2015-03-26 BR BR122023027559-4A patent/BR122023027559A2/pt not_active Application Discontinuation
- 2015-03-26 EP EP19205321.3A patent/EP3653644B1/en active Active
- 2015-03-26 RS RS20191652A patent/RS59700B1/sr unknown
- 2015-03-26 ES ES15712629T patent/ES2763859T3/es active Active
- 2015-03-26 PL PL19205321.3T patent/PL3653644T3/pl unknown
- 2015-03-26 SI SI201531059T patent/SI3122775T1/sl unknown
- 2015-03-26 WO PCT/EP2015/056654 patent/WO2015144855A1/en not_active Ceased
- 2015-03-26 LT LTEP19205321.3T patent/LT3653644T/lt unknown
- 2015-03-26 ES ES19205321T patent/ES2965626T3/es active Active
- 2015-03-26 KR KR1020167029710A patent/KR102520978B1/ko active Active
- 2015-03-26 PT PT157126293T patent/PT3122775T/pt unknown
-
2016
- 2016-09-26 IL IL248038A patent/IL248038B/en active IP Right Grant
-
2018
- 2018-03-05 US US15/912,358 patent/US10604565B2/en active Active
-
2020
- 2020-01-08 CY CY20201100008T patent/CY1122456T1/el unknown
- 2020-02-19 US US16/794,401 patent/US11634482B2/en active Active
- 2020-02-19 US US16/794,406 patent/US11760795B2/en active Active
- 2020-07-30 IL IL276405A patent/IL276405B/en unknown
- 2020-10-28 AU AU2020260440A patent/AU2020260440B2/en active Active
-
2021
- 2021-04-06 JP JP2021064572A patent/JP7607498B2/ja active Active
-
2023
- 2023-04-06 JP JP2023062338A patent/JP2023098966A/ja not_active Withdrawn
- 2023-08-02 US US18/364,173 patent/US20230382987A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7607498B2 (ja) | 成長分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体およびがん悪液質およびがんを処置するためのその使用 | |
| JP7270522B2 (ja) | 増殖分化因子１５（ｇｄｆ－１５）に対するモノクローナル抗体 | |
| GB2524552A (en) | Monoclonal antibodies to growth and differentiation factor 15 (GDF-15), and use thereof for treating cancer | |
| HK1231096B (en) | Monoclonal antibodies to growth and differentiation factor 15 (gdf-15), and uses thereof for treating cancer cachexia and cancer | |
| HK1231096A1 (en) | Monoclonal antibodies to growth and differentiation factor 15 (gdf-15), and uses thereof for treating cancer cachexia and cancer | |
| BR112016022013B1 (pt) | Anticorpos monoclonais que se ligam a gdf-15 humano e kit compreendendo os mesmos | |
| HK1210950B (en) | Monoclonal antibodies to growth and differentiation factor 15 (gdf-15) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20161121 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180326 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180326 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190122 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190301 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190530 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190823 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200120 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200420 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200904 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201126 |
|
| 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: 20210308 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210406 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6865585 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |