CN115605513A - 一种抗pd-l1和her2的双特异性抗体 - Google Patents
一种抗pd-l1和her2的双特异性抗体 Download PDFInfo
- Publication number
- CN115605513A CN115605513A CN202180032220.0A CN202180032220A CN115605513A CN 115605513 A CN115605513 A CN 115605513A CN 202180032220 A CN202180032220 A CN 202180032220A CN 115605513 A CN115605513 A CN 115605513A
- Authority
- CN
- China
- Prior art keywords
- seq
- amino acid
- cancer
- acid sequence
- her2
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 title claims abstract description 21
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 title claims abstract description 21
- 102000008096 B7-H1 Antigen Human genes 0.000 title claims abstract 7
- 108010074708 B7-H1 Antigen Proteins 0.000 title claims abstract 7
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 claims abstract description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 69
- 206010028980 Neoplasm Diseases 0.000 claims description 51
- 230000027455 binding Effects 0.000 claims description 39
- 238000009739 binding Methods 0.000 claims description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 27
- 229920001184 polypeptide Polymers 0.000 claims description 26
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 26
- 239000000427 antigen Substances 0.000 claims description 21
- 102000036639 antigens Human genes 0.000 claims description 20
- 108091007433 antigens Proteins 0.000 claims description 20
- 201000011510 cancer Diseases 0.000 claims description 15
- 239000013604 expression vector Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 206010009944 Colon cancer Diseases 0.000 claims description 8
- 208000029742 colonic neoplasm Diseases 0.000 claims description 8
- 230000035772 mutation Effects 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
- 208000032612 Glial tumor Diseases 0.000 claims description 5
- 206010018338 Glioma Diseases 0.000 claims description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 206010038389 Renal cancer Diseases 0.000 claims description 5
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 5
- 201000010881 cervical cancer Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 201000004101 esophageal cancer Diseases 0.000 claims description 5
- 201000010982 kidney cancer Diseases 0.000 claims description 5
- 201000007270 liver cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 230000003211 malignant effect Effects 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 230000001613 neoplastic effect Effects 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 2
- 230000009452 underexpressoin Effects 0.000 claims description 2
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 claims 1
- 101100454808 Caenorhabditis elegans lgg-2 gene Proteins 0.000 claims 1
- 101100217502 Caenorhabditis elegans lgg-3 gene Proteins 0.000 claims 1
- 230000004071 biological effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 65
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 23
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 17
- 238000002965 ELISA Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 230000004663 cell proliferation Effects 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 210000001744 T-lymphocyte Anatomy 0.000 description 13
- 102100020873 Interleukin-2 Human genes 0.000 description 11
- 108010002350 Interleukin-2 Proteins 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- 238000004113 cell culture Methods 0.000 description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 239000012980 RPMI-1640 medium Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 206010017758 gastric cancer Diseases 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 201000011549 stomach cancer Diseases 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000009036 growth inhibition Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000007865 diluting Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 238000003782 apoptosis assay Methods 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000006957 competitive inhibition Effects 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000011577 humanized mouse model Methods 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 230000005522 programmed cell death Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960000575 trastuzumab Drugs 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 2
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 210000005220 cytoplasmic tail Anatomy 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 241000218916 Cycas Species 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 230000009833 antibody interaction Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000182 cd11c+cd123- dc Anatomy 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- -1 etc. Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 102000048776 human CD274 Human genes 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000007898 magnetic cell sorting Methods 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 229940125645 monoclonal antibody drug Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000009707 neogenesis Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 201000002740 oral squamous cell carcinoma Diseases 0.000 description 1
- 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003442 weekly effect Effects 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- 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
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明提供了一种抗PD‑L1和HER2的双特异性抗体。本发明的双特异性抗体能够同时特异性结合PD‑L1和HER2两个靶点，具有与单抗相似甚至更优的生物学活性。
Description
PCT国内申请，说明书已公开。
Claims (17)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2020104876369 | 2020-06-02 | ||
| CN202010487636.9A CN113754775A (zh) | 2020-06-02 | 2020-06-02 | 一种抗pd-l1和her2的双特异性抗体 |
| PCT/CN2021/095189 WO2021244328A1 (zh) | 2020-06-02 | 2021-05-21 | 一种抗pd-l1和her2的双特异性抗体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115605513A true CN115605513A (zh) | 2023-01-13 |
| CN115605513B CN115605513B (zh) | 2024-03-19 |
Family
ID=78782246
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010487636.9A Pending CN113754775A (zh) | 2020-06-02 | 2020-06-02 | 一种抗pd-l1和her2的双特异性抗体 |
| CN202180032220.0A Active CN115605513B (zh) | 2020-06-02 | 2021-05-21 | 一种抗pd-l1和her2的双特异性抗体 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010487636.9A Pending CN113754775A (zh) | 2020-06-02 | 2020-06-02 | 一种抗pd-l1和her2的双特异性抗体 |
Country Status (3)
| Country | Link |
|---|---|
| CN (2) | CN113754775A (zh) |
| TW (1) | TW202146457A (zh) |
| WO (1) | WO2021244328A1 (zh) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021226984A1 (zh) * | 2020-05-15 | 2021-11-18 | 三生国健药业（上海）股份有限公司 | 一种抗pd-1和pd-l1的四价双特异性抗体 |
| CN113943371B (zh) * | 2021-11-01 | 2023-05-05 | 达石药业(广东)有限公司 | 一种抗her2/抗pd-l1双功能抗体及其应用 |
| CN114409797B (zh) * | 2021-12-24 | 2024-02-20 | 合肥天港免疫药物有限公司 | 重组抗体及其应用 |
| CN117247457A (zh) * | 2022-06-10 | 2023-12-19 | 三优生物医药(上海)有限公司 | 靶向her2和pd-l1的双特异性抗体及其制备方法和应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5821337A (en) * | 1991-06-14 | 1998-10-13 | Genentech, Inc. | Immunoglobulin variants |
| CN110790840A (zh) * | 2018-08-01 | 2020-02-14 | 三生国健药业（上海）股份有限公司 | 结合人her2的抗体、其制备方法和用途 |
| CN111196856A (zh) * | 2018-11-19 | 2020-05-26 | 三生国健药业（上海）股份有限公司 | 抗her2/pd1双特异性抗体 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3455257B1 (en) * | 2016-05-09 | 2021-09-22 | IGM Biosciences Inc. | Anti-pd-l1 antibodies |
| GB201611530D0 (en) * | 2016-07-01 | 2016-08-17 | Alligator Bioscience Ab | Novel polypeptides |
-
2020
- 2020-06-02 CN CN202010487636.9A patent/CN113754775A/zh active Pending
-
2021
- 2021-05-21 WO PCT/CN2021/095189 patent/WO2021244328A1/zh active Application Filing
- 2021-05-21 CN CN202180032220.0A patent/CN115605513B/zh active Active
- 2021-06-01 TW TW110119871A patent/TW202146457A/zh unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5821337A (en) * | 1991-06-14 | 1998-10-13 | Genentech, Inc. | Immunoglobulin variants |
| CN110790840A (zh) * | 2018-08-01 | 2020-02-14 | 三生国健药业（上海）股份有限公司 | 结合人her2的抗体、其制备方法和用途 |
| CN111196856A (zh) * | 2018-11-19 | 2020-05-26 | 三生国健药业（上海）股份有限公司 | 抗her2/pd1双特异性抗体 |
Non-Patent Citations (1)
| Title |
|---|
| DEEPAK MITTAL，ET AL.: "Blockade of ErbB2 and PD-L1 using a bispecific antibody to improve targeted anti-ErbB2 therapy", ONCOIMMUNOLOGY, vol. 8, no. 11, pages 1648171 - 2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115605513B (zh) | 2024-03-19 |
| CN113754775A (zh) | 2021-12-07 |
| WO2021244328A1 (zh) | 2021-12-09 |
| TW202146457A (zh) | 2021-12-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6224759B2 (ja) | 抗ｂ７−ｈ３抗体 | |
| EP3882275A1 (en) | Anti-pd-1 and anti-vegfa bifunctional antibody, pharmaceutical composition thereof and use thereof | |
| JP6124377B2 (ja) | 新規抗ｄｒ５抗体 | |
| US9808507B2 (en) | Anti-c-Met/anti-Ang2 bispecific antibody | |
| CN115605513B (zh) | 一种抗pd-l1和her2的双特异性抗体 | |
| JP2015024994A (ja) | ＤＡＲＰｉｎを含む二重特異キメラ蛋白質 | |
| CA2851135A1 (en) | Anti c-met antibody and uses thereof | |
| WO2020025013A1 (zh) | 结合人her2的抗体、其制备方法和用途 | |
| AU2017358359B2 (en) | Antibody binding specifically to CD66c and use thereof | |
| JP7397897B2 (ja) | ヒトｐｄ－ｌ１に結合する抗体 | |
| EP4039704A1 (en) | Anti-pd-1 antibody and use thereof | |
| WO2022194201A1 (zh) | 一种靶向cldn18.2的抗体或其抗原结合片段及其应用 | |
| WO2020063660A1 (zh) | 抗ox40抗体、其抗原结合片段及其医药用途 | |
| US20240343803A1 (en) | Anti-Pvrig/Anti-Tigit Bispecific Antibodies And Applications Thereof | |
| US20230257465A1 (en) | ANTI-PDL1 x EGFR BISPECIFIC ANTIBODY | |
| US20230174670A1 (en) | Anti-cd25 antibodies, antigen-binding fragments thereof, and medical uses thereof | |
| US20210024638A1 (en) | Anti-egfr/anti-4-1bb bispecific antibody and use thereof | |
| JP2023505123A (ja) | 医薬組成物、その製造方法及び用途 | |
| EP4435010A1 (en) | Bispecific antibody against tigit and pd-l1, and pharmaceutical composition thereof and use thereof | |
| EP3086808B1 (en) | Anti adam17 antibody and its use for the treatment of cancer | |
| CN116284408A (zh) | 结合人muc17的抗体、其制备方法及用途 | |
| TW202208438A (zh) | 抗ｌｉｌｒｂ１抗體或其抗原結合片段、製備其的方法、藥物組成物、核酸分子、重組載體以及重組細胞 | |
| CN115667315A (zh) | 一种抗pd1×pdl1的双特异性抗体 | |
| WO2021013061A1 (zh) | 一种人源化抗vegfr2抗体及其应用 | |
| RU2809746C2 (ru) | Гуманизированное моноклональное антитело против vegf |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |