JP7330942B2 - 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 - Google Patents
二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 Download PDFInfo
- Publication number
- JP7330942B2 JP7330942B2 JP2020503365A JP2020503365A JP7330942B2 JP 7330942 B2 JP7330942 B2 JP 7330942B2 JP 2020503365 A JP2020503365 A JP 2020503365A JP 2020503365 A JP2020503365 A JP 2020503365A JP 7330942 B2 JP7330942 B2 JP 7330942B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- antibody
- set forth
- sequence set
- igg1
- 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
- 238000000034 method Methods 0.000 title claims description 65
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims description 331
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims description 289
- 210000004027 cell Anatomy 0.000 claims description 258
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims description 248
- 230000035772 mutation Effects 0.000 claims description 213
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims description 205
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 claims description 203
- 239000000427 antigen Substances 0.000 claims description 203
- 108091007433 antigens Proteins 0.000 claims description 203
- 102000036639 antigens Human genes 0.000 claims description 203
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 claims description 202
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 claims description 202
- 241000282414 Homo sapiens Species 0.000 claims description 145
- 238000006467 substitution reaction Methods 0.000 claims description 143
- 230000003993 interaction Effects 0.000 claims description 105
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 claims description 86
- 102000048426 human CD37 Human genes 0.000 claims description 83
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 72
- 230000002708 enhancing effect Effects 0.000 claims description 56
- 206010028980 Neoplasm Diseases 0.000 claims description 43
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 40
- 241000282567 Macaca fascicularis Species 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 36
- 239000003814 drug Substances 0.000 claims description 32
- 150000007523 nucleic acids Chemical class 0.000 claims description 29
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 claims description 25
- 201000003444 follicular lymphoma Diseases 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 24
- 108020004707 nucleic acids Proteins 0.000 claims description 24
- 108060003951 Immunoglobulin Proteins 0.000 claims description 23
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 23
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 23
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 23
- 102000018358 immunoglobulin Human genes 0.000 claims description 23
- 238000000338 in vitro Methods 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 21
- 239000013604 expression vector Substances 0.000 claims description 20
- 229960002450 ofatumumab Drugs 0.000 claims description 20
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 19
- 239000012636 effector Substances 0.000 claims description 19
- 229940124597 therapeutic agent Drugs 0.000 claims description 19
- 229960004641 rituximab Drugs 0.000 claims description 18
- 230000036210 malignancy Effects 0.000 claims description 17
- 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 16
- 208000031223 plasma cell leukemia Diseases 0.000 claims description 16
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims description 9
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 9
- 206010020751 Hypersensitivity Diseases 0.000 claims description 9
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 9
- 206010052779 Transplant rejections Diseases 0.000 claims description 9
- 230000007815 allergy Effects 0.000 claims description 9
- 229960004397 cyclophosphamide Drugs 0.000 claims description 9
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims description 9
- 229960001507 ibrutinib Drugs 0.000 claims description 9
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 8
- 208000026935 allergic disease Diseases 0.000 claims description 8
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 claims description 8
- 229960002707 bendamustine Drugs 0.000 claims description 8
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 8
- 229960004630 chlorambucil Drugs 0.000 claims description 8
- 229960004679 doxorubicin Drugs 0.000 claims description 8
- 229960000390 fludarabine Drugs 0.000 claims description 8
- 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 8
- 229960004528 vincristine Drugs 0.000 claims description 8
- 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 8
- 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 8
- 108010006654 Bleomycin Proteins 0.000 claims description 7
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 7
- 229960001561 bleomycin Drugs 0.000 claims description 7
- 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 7
- 229960005243 carmustine Drugs 0.000 claims description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 7
- 229960004316 cisplatin Drugs 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 230000000813 microbial effect Effects 0.000 claims description 2
- 235000001014 amino acid Nutrition 0.000 description 160
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 118
- 125000003275 alpha amino acid group Chemical group 0.000 description 96
- 229940024606 amino acid Drugs 0.000 description 85
- 150000001413 amino acids Chemical class 0.000 description 78
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 73
- 230000000875 corresponding effect Effects 0.000 description 43
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 38
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 37
- 210000004881 tumor cell Anatomy 0.000 description 37
- 238000000684 flow cytometry Methods 0.000 description 36
- 108090000623 proteins and genes Proteins 0.000 description 36
- 210000004369 blood Anatomy 0.000 description 32
- 239000008280 blood Substances 0.000 description 32
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 31
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 30
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 28
- 230000014509 gene expression Effects 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 26
- 102000004169 proteins and genes Human genes 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 230000003389 potentiating effect Effects 0.000 description 23
- 239000013598 vector Substances 0.000 description 23
- 230000009089 cytolysis Effects 0.000 description 22
- 230000001404 mediated effect Effects 0.000 description 22
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 20
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 19
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- 241000283973 Oryctolagus cuniculus Species 0.000 description 19
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 18
- 229940098773 bovine serum albumin Drugs 0.000 description 18
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 17
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 17
- 125000000539 amino acid group Chemical group 0.000 description 16
- 235000004279 alanine Nutrition 0.000 description 15
- 230000009977 dual effect Effects 0.000 description 15
- 239000012634 fragment Substances 0.000 description 15
- 230000004927 fusion Effects 0.000 description 15
- 206010003246 arthritis Diseases 0.000 description 14
- 239000000872 buffer Substances 0.000 description 14
- 230000000295 complement effect Effects 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 230000003013 cytotoxicity Effects 0.000 description 13
- 231100000135 cytotoxicity Toxicity 0.000 description 13
- 238000005516 engineering process Methods 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 238000011534 incubation Methods 0.000 description 13
- 230000006698 induction Effects 0.000 description 13
- 229960003347 obinutuzumab Drugs 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- 231100000673 dose–response relationship Toxicity 0.000 description 12
- 230000001939 inductive effect Effects 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 210000004602 germ cell Anatomy 0.000 description 11
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 10
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 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 9
- 208000003950 B-cell lymphoma Diseases 0.000 description 9
- 201000005569 Gout Diseases 0.000 description 9
- 201000008482 osteoarthritis Diseases 0.000 description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- -1 FR3 Proteins 0.000 description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 8
- QHNORJFCVHUPNH-UHFFFAOYSA-L To-Pro-3 Chemical compound [I-].[I-].S1C2=CC=CC=C2[N+](C)=C1C=CC=C1C2=CC=CC=C2N(CCC[N+](C)(C)C)C=C1 QHNORJFCVHUPNH-UHFFFAOYSA-L 0.000 description 8
- 235000018417 cysteine Nutrition 0.000 description 8
- 230000003211 malignant effect Effects 0.000 description 8
- 230000036515 potency Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 7
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 7
- 239000012980 RPMI-1640 medium Substances 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000011533 pre-incubation Methods 0.000 description 7
- 238000013207 serial dilution Methods 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 102100022002 CD59 glycoprotein Human genes 0.000 description 6
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 206010018634 Gouty Arthritis Diseases 0.000 description 6
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 6
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 6
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 6
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 6
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 6
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 6
- 102100039373 Membrane cofactor protein Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 206010036105 Polyneuropathy Diseases 0.000 description 6
- 239000004793 Polystyrene Substances 0.000 description 6
- 206010037575 Pustular psoriasis Diseases 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 229920002223 polystyrene Polymers 0.000 description 6
- 201000010914 pustulosis of palm and sole Diseases 0.000 description 6
- 208000011797 pustulosis palmaris et plantaris Diseases 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 238000011579 SCID mouse model Methods 0.000 description 5
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 5
- 230000029918 bioluminescence Effects 0.000 description 5
- 238000005415 bioluminescence Methods 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 230000004186 co-expression Effects 0.000 description 5
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 5
- 150000001945 cysteines Chemical class 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 210000004408 hybridoma Anatomy 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229960003151 mercaptamine Drugs 0.000 description 5
- 239000004175 ponceau 4R Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- 239000012103 Alexa Fluor 488 Substances 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VYZAMTAEIAYCRO-BJUDXGSMSA-N Chromium-51 Chemical compound [51Cr] VYZAMTAEIAYCRO-BJUDXGSMSA-N 0.000 description 4
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical compound N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000833 heterodimer Substances 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229920009537 polybutylene succinate adipate Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin 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)=C(N)C=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 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 3
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 3
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 3
- 208000011691 Burkitt lymphomas Diseases 0.000 description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 102000000503 Collagen Type II Human genes 0.000 description 3
- 108010041390 Collagen Type II Proteins 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 206010012438 Dermatitis atopic Diseases 0.000 description 3
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 3
- 102000007625 Hirudins Human genes 0.000 description 3
- 108010007267 Hirudins Proteins 0.000 description 3
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 3
- 206010021263 IgA nephropathy Diseases 0.000 description 3
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 3
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 3
- 208000004575 Infectious Arthritis Diseases 0.000 description 3
- 208000003456 Juvenile Arthritis Diseases 0.000 description 3
- 208000016604 Lyme disease Diseases 0.000 description 3
- 241001436793 Meru Species 0.000 description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 241000721454 Pemphigus Species 0.000 description 3
- 206010036030 Polyarthritis Diseases 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 3
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 3
- 208000003782 Raynaud disease Diseases 0.000 description 3
- 208000012322 Raynaud phenomenon Diseases 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- 208000026816 acute arthritis Diseases 0.000 description 3
- 238000012867 alanine scanning Methods 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- 201000008937 atopic dermatitis Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 238000012575 bio-layer interferometry Methods 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000011651 chromium Substances 0.000 description 3
- 208000019069 chronic childhood arthritis Diseases 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000024203 complement activation Effects 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 230000003628 erosive effect Effects 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 229940006607 hirudin Drugs 0.000 description 3
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 201000011486 lichen planus Diseases 0.000 description 3
- 239000003068 molecular probe Substances 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 206010028417 myasthenia gravis Diseases 0.000 description 3
- 238000006384 oligomerization reaction Methods 0.000 description 3
- 230000007824 polyneuropathy Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 201000001223 septic arthritis Diseases 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 201000005671 spondyloarthropathy Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229960001183 venetoclax Drugs 0.000 description 3
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- WLKSPGHQGFFKGE-UHFFFAOYSA-N 1-chloropropan-2-yl n-(3-chlorophenyl)carbamate Chemical compound ClCC(C)OC(=O)NC1=CC=CC(Cl)=C1 WLKSPGHQGFFKGE-UHFFFAOYSA-N 0.000 description 2
- 240000005020 Acaciella glauca Species 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 241000239226 Scorpiones Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 108700042805 TRU-015 Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000009830 antibody antigen interaction Effects 0.000 description 2
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000004154 complement system Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 239000000562 conjugate Substances 0.000 description 2
- 208000010247 contact dermatitis Diseases 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- CEJLBZWIKQJOAT-UHFFFAOYSA-N dichloroisocyanuric acid Chemical compound ClN1C(=O)NC(=O)N(Cl)C1=O CEJLBZWIKQJOAT-UHFFFAOYSA-N 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 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 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000005734 heterodimerization reaction Methods 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229950001237 lilotomab Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- ANZJBCHSOXCCRQ-FKUXLPTCSA-N mertansine Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCS)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 ANZJBCHSOXCCRQ-FKUXLPTCSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229950005751 ocrelizumab Drugs 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 208000019629 polyneuritis Diseases 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 231100001271 preclinical toxicology Toxicity 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 229950000815 veltuzumab Drugs 0.000 description 2
- ZTOJFFHGPLIVKC-YAFCTCPESA-N (2e)-3-ethyl-2-[(z)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S\1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C/1=N/N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-YAFCTCPESA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-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
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- ZTOJFFHGPLIVKC-UHFFFAOYSA-N 3-ethyl-2-[(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C1=NN=C1SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-UHFFFAOYSA-N 0.000 description 1
- 229940127148 AGS67E Drugs 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 108010025188 Alcohol oxidase Proteins 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 101150066967 CD37 gene Proteins 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 241000256135 Chironomus thummi Species 0.000 description 1
- 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 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- 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 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 101100012887 Drosophila melanogaster btl gene Proteins 0.000 description 1
- 101100012878 Drosophila melanogaster htl gene Proteins 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
- 238000002965 ELISA Methods 0.000 description 1
- 102000000579 Epigen Human genes 0.000 description 1
- 108010016906 Epigen Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 1
- 101000830565 Homo sapiens Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 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 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 101710146560 Leukocyte antigen CD37 Proteins 0.000 description 1
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 229910052765 Lutetium Inorganic materials 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 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 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000001825 Polyoxyethene (8) stearate Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 102000043977 Tetraspanins Human genes 0.000 description 1
- 108700031126 Tetraspanins Proteins 0.000 description 1
- 102100031013 Transgelin Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- WDENQIQQYWYTPO-IBGZPJMESA-N acalabrutinib Chemical compound CC#CC(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C(=O)NC=2N=CC=CC=2)=C2N1C=CN=C2N WDENQIQQYWYTPO-IBGZPJMESA-N 0.000 description 1
- 229950009821 acalabrutinib Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 150000001295 alanines Chemical group 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 description 1
- 229960003094 belinostat Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000003618 borate buffered saline Substances 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229950002550 copanlisib Drugs 0.000 description 1
- PZBCKZWLPGJMAO-UHFFFAOYSA-N copanlisib Chemical compound C1=CC=2C3=NCCN3C(NC(=O)C=3C=NC(N)=NC=3)=NC=2C(OC)=C1OCCCN1CCOCC1 PZBCKZWLPGJMAO-UHFFFAOYSA-N 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000000375 direct analysis in real time Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 238000012063 dual-affinity re-targeting Methods 0.000 description 1
- 230000001094 effect on targets Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 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 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 125000003712 glycosamine group Chemical group 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 102000044949 human TNFSF10 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229960003445 idelalisib Drugs 0.000 description 1
- YKLIKGKUANLGSB-HNNXBMFYSA-N idelalisib Chemical compound C1([C@@H](NC=2[C]3N=CN=C3N=CN=2)CC)=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1 YKLIKGKUANLGSB-HNNXBMFYSA-N 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940004975 interceptor Drugs 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 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 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960004942 lenalidomide Drugs 0.000 description 1
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 1
- 238000002898 library design Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000004337 magnesium citrate Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960005558 mertansine Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 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
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 239000012514 monoclonal antibody product Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 108010093470 monomethyl auristatin E Proteins 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 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 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000003711 photoprotective effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 208000000813 polyradiculoneuropathy Diseases 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- OGSBUKJUDHAQEA-WMCAAGNKSA-N pralatrexate Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CC(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OGSBUKJUDHAQEA-WMCAAGNKSA-N 0.000 description 1
- 229960000214 pralatrexate Drugs 0.000 description 1
- 238000012910 preclinical development Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229940051022 radioimmunoconjugate Drugs 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960003452 romidepsin Drugs 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 description 1
- 108010091666 romidepsin Proteins 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 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 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 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 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000014723 transformation of host cell by virus Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 1
- 229960000237 vorinostat Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- 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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- 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
- C07K2317/72—Increased effector function due to an Fc-modification
-
- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- 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
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023130372A JP7680501B2 (ja) | 2017-03-31 | 2023-08-09 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
| JP2025078106A JP2025121994A (ja) | 2017-03-31 | 2025-05-08 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762479712P | 2017-03-31 | 2017-03-31 | |
| US62/479,712 | 2017-03-31 | ||
| EP2018057836 | 2018-03-27 | ||
| EPPCT/EP2018/057836 | 2018-03-27 | ||
| PCT/EP2018/058479 WO2018178396A1 (en) | 2017-03-31 | 2018-04-03 | Bispecific anti-cd37 antibodies, monoclonal anti-cd37 antibodies and methods of use thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023130372A Division JP7680501B2 (ja) | 2017-03-31 | 2023-08-09 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020516309A JP2020516309A (ja) | 2020-06-11 |
| JP2020516309A5 JP2020516309A5 (enExample) | 2021-05-13 |
| JP7330942B2 true JP7330942B2 (ja) | 2023-08-22 |
Family
ID=62044657
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020503365A Active JP7330942B2 (ja) | 2017-03-31 | 2018-04-03 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
| JP2023130372A Active JP7680501B2 (ja) | 2017-03-31 | 2023-08-09 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
| JP2025078106A Pending JP2025121994A (ja) | 2017-03-31 | 2025-05-08 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023130372A Active JP7680501B2 (ja) | 2017-03-31 | 2023-08-09 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
| JP2025078106A Pending JP2025121994A (ja) | 2017-03-31 | 2025-05-08 | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (7) | US20200270359A1 (enExample) |
| EP (1) | EP3601354A1 (enExample) |
| JP (3) | JP7330942B2 (enExample) |
| KR (1) | KR102706161B1 (enExample) |
| CN (2) | CN119285787A (enExample) |
| AU (2) | AU2018242227B2 (enExample) |
| BR (1) | BR112019020219A2 (enExample) |
| CA (1) | CA3057907A1 (enExample) |
| IL (1) | IL269645B2 (enExample) |
| MX (2) | MX2019011520A (enExample) |
| SG (1) | SG11201908772TA (enExample) |
| UA (1) | UA127586C2 (enExample) |
| WO (1) | WO2018178396A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA117901C2 (uk) * | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
| KR102706161B1 (ko) | 2017-03-31 | 2024-09-19 | 젠맵 홀딩 비.브이. | 이중특이적 항-cd37 항체, 모노클로날 항-cd37 항체 및 그의 사용 방법 |
| US12227567B2 (en) | 2017-07-25 | 2025-02-18 | Truebinding, Inc. | Treating cancer by blocking the interaction of TIM-3 and its ligand |
| BR112020022179A2 (pt) | 2018-05-03 | 2021-02-02 | Genmab B.V. | primeiro anticorpo, anticorpo, composição, métodos para tratar um indivíduo tendo uma doença, para esgotar uma população de célula e para induzir a proliferação em uma população de célula, e, kit. |
| JP7513530B2 (ja) * | 2018-06-22 | 2024-07-09 | ジェンマブ ホールディング ビー．ブイ． | 抗ｃｄ３７抗体および抗ｃｄ２０抗体、組成物、ならびにそれらの使用方法 |
| EP3860715A1 (en) * | 2018-10-04 | 2021-08-11 | Genmab Holding B.V. | Pharmaceutical compositions comprising bispecific anti-cd37 antibodies |
| WO2020146267A1 (en) * | 2019-01-11 | 2020-07-16 | Promab Biotechnologies, Inc. | Cd37-antibody and cd37-car-t cells |
| CN116063520A (zh) | 2019-01-30 | 2023-05-05 | 真和制药有限公司 | 抗gal3抗体及其用途 |
| CN116157151A (zh) | 2020-05-26 | 2023-05-23 | 真和制药有限公司 | 通过阻断半乳凝素-3治疗炎性疾病的方法 |
| CN113504371B (zh) * | 2021-07-09 | 2024-06-14 | 博以新(杭州)生物技术有限公司 | 基于环糊精包合的免分离化学发光免疫分析的方法 |
| JP7437558B1 (ja) | 2023-07-20 | 2024-02-22 | 株式会社ファーマフーズ | 情報処理装置、情報処理方法、およびプログラム |
| WO2025083205A1 (en) | 2023-10-18 | 2025-04-24 | Debiopharm International S.A. | Drug combination comprising anti-cd37 antibody maytansine conjugate and bcl2 inhibitor or pi3k inhibitor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009539413A (ja) | 2006-06-12 | 2009-11-19 | トゥルビオン・ファーマシューティカルズ・インコーポレーテッド | エフェクター機能を有する単鎖多価結合タンパク質 |
| JP2013524777A (ja) | 2010-03-12 | 2013-06-20 | イミュノジェン， インコーポレイテッド | Ｃｄ３７結合分子及びそのイムノコンジュゲート |
| JP2016509476A (ja) | 2013-01-10 | 2016-03-31 | ゲンマブ ビー．ブイ． | ヒトＩｇＧ１Ｆｃ領域変異体およびその使用 |
Family Cites Families (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| EP0940468A1 (en) | 1991-06-14 | 1999-09-08 | Genentech, Inc. | Humanized antibody variable domain |
| GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
| US6077835A (en) | 1994-03-23 | 2000-06-20 | Case Western Reserve University | Delivery of compacted nucleic acid to cells |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| KR970029803A (ko) | 1995-11-03 | 1997-06-26 | 김광호 | 반도체 메모리장치의 프리차지 회로 |
| AU751659B2 (en) | 1997-05-02 | 2002-08-22 | Genentech Inc. | A method for making multispecific antibodies having heteromultimeric and common components |
| US6355271B1 (en) | 1999-02-03 | 2002-03-12 | Biosante Pharmaceuticals, Inc. | Therapeutic calcium phosphate particles and methods of manufacture and use |
| US6281005B1 (en) | 1999-05-14 | 2001-08-28 | Copernicus Therapeutics, Inc. | Automated nucleic acid compaction device |
| DE10043437A1 (de) | 2000-09-04 | 2002-03-28 | Horst Lindhofer | Verwendung von trifunktionellen bispezifischen und trispezifischen Antikörpern zur Behandlung von malignem Aszites |
| US20030103971A1 (en) | 2001-11-09 | 2003-06-05 | Kandasamy Hariharan | Immunoregulatory antibodies and uses thereof |
| US20100081792A1 (en) | 2001-06-28 | 2010-04-01 | Smithkline Beecham Corporation | Ligand |
| AU2003209446B2 (en) | 2002-03-01 | 2008-09-25 | Immunomedics, Inc. | Bispecific antibody point mutations for enhancing rate of clearance |
| AU2003250074B2 (en) | 2002-07-18 | 2010-09-09 | Merus N.V. | Recombinant production of mixtures of antibodies |
| KR100932340B1 (ko) | 2002-10-17 | 2009-12-16 | 젠맵 에이/에스 | Ｃｄ20에 대한 인간 모노클로날 항체 |
| EP1638510B1 (en) | 2003-07-01 | 2015-09-02 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
| EP1740946B1 (en) | 2004-04-20 | 2013-11-06 | Genmab A/S | Human monoclonal antibodies against cd20 |
| US7741568B2 (en) | 2005-01-13 | 2010-06-22 | The Wiremold Company | Downward facing receptacle assembly for cable raceway |
| EP3050963B1 (en) | 2005-03-31 | 2019-09-18 | Chugai Seiyaku Kabushiki Kaisha | Process for production of polypeptide by regulation of assembly |
| SI1912675T1 (sl) * | 2005-07-25 | 2014-07-31 | Emergent Product Development Seattle, Llc | zmanjšanje števila celic B z uporabo molekul, ki se specifično vežejo na CD37 in CD20 |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| US10155816B2 (en) | 2005-11-28 | 2018-12-18 | Genmab A/S | Recombinant monovalent antibodies and methods for production thereof |
| AU2007227292B2 (en) | 2006-03-17 | 2012-04-12 | Biogen Ma Inc. | Stabilized polypeptide compositions |
| CA2646965C (en) | 2006-03-24 | 2016-06-21 | Jonathan H. Davis | Engineered heterodimeric protein domains |
| AT503902B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von immunglobulinen |
| ES2667863T3 (es) | 2007-03-29 | 2018-05-14 | Genmab A/S | Anticuerpos biespecíficos y métodos de producción de los mismos |
| KR101799337B1 (ko) | 2007-06-21 | 2017-12-20 | 마크로제닉스, 인크. | 공유결합형 디아바디 및 이것의 사용 |
| PE20140196A1 (es) * | 2007-08-09 | 2014-03-19 | Boehringer Ingelheim Int | Anticuerpos anti-cd37 |
| CA2700714C (en) | 2007-09-26 | 2018-09-11 | Ucb Pharma S.A. | Dual specificity antibody fusions |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US8242247B2 (en) | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
| US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
| US8227577B2 (en) | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| ES2563027T3 (es) | 2008-01-07 | 2016-03-10 | Amgen Inc. | Método para fabricación de moléculas heterodímeras Fc de anticuerpos utilizando efectos de conducción electrostática |
| SG189772A1 (en) | 2008-04-11 | 2013-05-31 | Trubion Pharmaceuticals Inc | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
| WO2010015792A1 (en) | 2008-08-06 | 2010-02-11 | Argenta Discovery Limited | Nitrogen containing heterocyclic compounds useful as bifunctional modulators of m3 receptors and beta-2 receptors |
| JP5397668B2 (ja) | 2008-09-02 | 2014-01-22 | ソニー株式会社 | 記憶素子および記憶装置 |
| SG10201407908VA (en) | 2008-12-19 | 2015-01-29 | Macrogenics Inc | Covalent diabodies and uses thereof |
| JP2012521768A (ja) | 2009-03-27 | 2012-09-20 | ジモジェネティクス・インコーポレイテッド | 抗体−受容体の組み合わせを含む多特異的結合性タンパク質を用いるための組成物および方法 |
| EP2424567B1 (en) | 2009-04-27 | 2018-11-21 | OncoMed Pharmaceuticals, Inc. | Method for making heteromultimeric molecules |
| KR101224468B1 (ko) | 2009-05-20 | 2013-01-23 | 주식회사 파멥신 | 신규한 형태의 이중표적항체 및 그 용도 |
| MX368932B (es) | 2009-06-26 | 2019-10-22 | Regeneron Pharma | Anticuerpos biespecificos facilmente aislados con formato de inmunoglobulina original. |
| US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| CN102770456B (zh) | 2009-12-04 | 2018-04-06 | 弗·哈夫曼-拉罗切有限公司 | 多特异性抗体、抗体类似物、组合物和方法 |
| AR080794A1 (es) | 2010-03-26 | 2012-05-09 | Hoffmann La Roche | Anticuerpos bivalentes biespecificos anti- vegf/ anti-ang-2 |
| US9150663B2 (en) | 2010-04-20 | 2015-10-06 | Genmab A/S | Heterodimeric antibody Fc-containing proteins and methods for production thereof |
| WO2011143545A1 (en) | 2010-05-14 | 2011-11-17 | Rinat Neuroscience Corporation | Heterodimeric proteins and methods for producing and purifying them |
| US20120189618A1 (en) | 2010-07-16 | 2012-07-26 | Boehringer Ingelheim International Gmbh | Superior efficacy of cd37 antibodies in cll blood samples |
| JP5997154B2 (ja) | 2010-08-16 | 2016-09-28 | ノビミューン エスアー | 多重特異性多価抗体の生成方法 |
| RU2013110876A (ru) | 2010-08-24 | 2014-09-27 | Рош Гликарт Аг | Активируемые биспецифические антитела |
| WO2012025530A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
| RU2604490C2 (ru) | 2010-11-05 | 2016-12-10 | Займворкс Инк. | ДИЗАЙН УСТОЙЧИВОГО ГЕТЕРОДИМЕРНОГО АНТИТЕЛА С МУТАЦИЯМИ В Fc ДОМЕНЕ |
| EP2694105A4 (en) | 2011-04-01 | 2015-04-29 | Immunogen Inc | CD37 BINDING MOLECULES AND IMMUNOCONJUGATES THEREOF |
| CN102250246A (zh) | 2011-06-10 | 2011-11-23 | 常州亚当生物技术有限公司 | 抗VEGF/PDGFRβ双特异性抗体及其应用 |
| UA117901C2 (uk) | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
| SI2771364T1 (sl) | 2011-10-27 | 2019-10-30 | Genmab As | Produkcija heterodimernih proteinov |
| PL2794905T3 (pl) | 2011-12-20 | 2020-11-02 | Medimmune, Llc | Zmodyfikowane polipeptydy dla rusztowań przeciwciał dwuswoistych |
| CN120383672A (zh) | 2012-04-20 | 2025-07-29 | 美勒斯公司 | 用于产生免疫球蛋白样分子的方法和手段 |
| US8992915B2 (en) * | 2012-05-16 | 2015-03-31 | Boehringer Ingelheim International Gmbh | Combination of CD37 antibodies with ICE |
| JP6514103B2 (ja) * | 2012-07-06 | 2019-05-15 | ゲンマブ ビー．ブイ． | 三重変異を有する二量体タンパク質 |
| WO2014081202A1 (ko) | 2012-11-21 | 2014-05-30 | 주식회사 파멥신 | Vegfr-2와 dll4를 표적으로 하는 이중표적항체 및 이를 포함하는 약학적 조성물 |
| CN105722534B (zh) * | 2013-08-01 | 2019-05-31 | 艾更斯司股份有限公司 | 结合cd37蛋白的抗体药物偶联物(adc) |
| US9650441B2 (en) | 2015-09-21 | 2017-05-16 | Erasmus University Medical Center | Anti-CD47 antibodies and methods of use |
| US20230399414A1 (en) | 2017-03-31 | 2023-12-14 | Genmab Holding B.V, | Bispecific anti-cd37 antibodies, monoclonal anti-cd37 antibodies and methods of use thereof |
| KR102706161B1 (ko) | 2017-03-31 | 2024-09-19 | 젠맵 홀딩 비.브이. | 이중특이적 항-cd37 항체, 모노클로날 항-cd37 항체 및 그의 사용 방법 |
| JP7513530B2 (ja) | 2018-06-22 | 2024-07-09 | ジェンマブ ホールディング ビー．ブイ． | 抗ｃｄ３７抗体および抗ｃｄ２０抗体、組成物、ならびにそれらの使用方法 |
-
2018
- 2018-04-03 KR KR1020197032125A patent/KR102706161B1/ko active Active
- 2018-04-03 SG SG11201908772T patent/SG11201908772TA/en unknown
- 2018-04-03 AU AU2018242227A patent/AU2018242227B2/en active Active
- 2018-04-03 IL IL269645A patent/IL269645B2/en unknown
- 2018-04-03 EP EP18719454.3A patent/EP3601354A1/en active Pending
- 2018-04-03 US US16/498,104 patent/US20200270359A1/en not_active Abandoned
- 2018-04-03 UA UAA201910706A patent/UA127586C2/uk unknown
- 2018-04-03 CN CN202411136586.4A patent/CN119285787A/zh active Pending
- 2018-04-03 JP JP2020503365A patent/JP7330942B2/ja active Active
- 2018-04-03 BR BR112019020219-6A patent/BR112019020219A2/pt unknown
- 2018-04-03 MX MX2019011520A patent/MX2019011520A/es unknown
- 2018-04-03 WO PCT/EP2018/058479 patent/WO2018178396A1/en not_active Ceased
- 2018-04-03 CN CN201880032561.6A patent/CN110914301B/zh active Active
- 2018-04-03 CA CA3057907A patent/CA3057907A1/en active Pending
-
2019
- 2019-09-26 MX MX2023011121A patent/MX2023011121A/es unknown
-
2020
- 2020-05-11 US US16/872,140 patent/US11512137B2/en active Active
- 2020-10-08 US US17/066,190 patent/US11034772B2/en active Active
-
2021
- 2021-07-22 US US17/382,758 patent/US11396553B2/en active Active
- 2021-11-23 US US17/534,029 patent/US12448459B2/en active Active
-
2022
- 2022-10-27 US US17/975,362 patent/US20240117064A1/en not_active Abandoned
-
2023
- 2023-08-09 JP JP2023130372A patent/JP7680501B2/ja active Active
- 2023-10-27 US US17/975,353 patent/US20240076397A1/en active Pending
-
2025
- 2025-05-08 JP JP2025078106A patent/JP2025121994A/ja active Pending
- 2025-06-13 AU AU2025204448A patent/AU2025204448A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009539413A (ja) | 2006-06-12 | 2009-11-19 | トゥルビオン・ファーマシューティカルズ・インコーポレーテッド | エフェクター機能を有する単鎖多価結合タンパク質 |
| JP2013524777A (ja) | 2010-03-12 | 2013-06-20 | イミュノジェン， インコーポレイテッド | Ｃｄ３７結合分子及びそのイムノコンジュゲート |
| JP2016509476A (ja) | 2013-01-10 | 2016-03-31 | ゲンマブ ビー．ブイ． | ヒトＩｇＧ１Ｆｃ領域変異体およびその使用 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7680501B2 (ja) | 二重特異性抗ｃｄ３７抗体、モノクローナル抗ｃｄ３７抗体、およびそれらの使用方法 | |
| EP3233907B1 (en) | Rodent bispecific heterodimeric proteins | |
| US11130819B2 (en) | Antibodies | |
| US20230399414A1 (en) | Bispecific anti-cd37 antibodies, monoclonal anti-cd37 antibodies and methods of use thereof | |
| JP7522106B2 (ja) | 二重特異性抗ｃｄ３７抗体を含む医薬組成物 | |
| JP7513530B2 (ja) | 抗ｃｄ３７抗体および抗ｃｄ２０抗体、組成物、ならびにそれらの使用方法 | |
| JP7791229B2 (ja) | 抗体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210401 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210401 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20210708 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20220131 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220221 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220517 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220719 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220822 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221024 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230120 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230420 |
|
| 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: 20230615 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230714 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230809 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7330942 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |