CN114502592A - 靶向cldn18.2的抗体及其制备方法和应用 - Google Patents
靶向cldn18.2的抗体及其制备方法和应用 Download PDFInfo
- Publication number
- CN114502592A CN114502592A CN202080068747.4A CN202080068747A CN114502592A CN 114502592 A CN114502592 A CN 114502592A CN 202080068747 A CN202080068747 A CN 202080068747A CN 114502592 A CN114502592 A CN 114502592A
- Authority
- CN
- China
- Prior art keywords
- seq
- amino acid
- acid sequence
- antibody
- variant
- 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
- 230000008685 targeting Effects 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims description 16
- 230000027455 binding Effects 0.000 claims abstract description 73
- 239000000427 antigen Substances 0.000 claims abstract description 47
- 102000036639 antigens Human genes 0.000 claims abstract description 47
- 108091007433 antigens Proteins 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 42
- 239000012634 fragment Substances 0.000 claims abstract description 40
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 261
- 210000004027 cell Anatomy 0.000 claims description 211
- 206010028980 Neoplasm Diseases 0.000 claims description 50
- 230000035772 mutation Effects 0.000 claims description 50
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 32
- 239000000611 antibody drug conjugate Substances 0.000 claims description 29
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 29
- 229940127089 cytotoxic agent Drugs 0.000 claims description 23
- 102000039446 nucleic acids Human genes 0.000 claims description 19
- 108020004707 nucleic acids Proteins 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 17
- 239000013598 vector Substances 0.000 claims description 17
- 239000013604 expression vector Substances 0.000 claims description 15
- 230000000259 anti-tumor effect Effects 0.000 claims description 14
- 239000002254 cytotoxic agent Substances 0.000 claims description 14
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 14
- 239000013612 plasmid Substances 0.000 claims description 14
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical group CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims description 13
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 13
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 12
- 206010017758 gastric cancer Diseases 0.000 claims description 12
- 238000003259 recombinant expression Methods 0.000 claims description 12
- 201000011549 stomach cancer Diseases 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 210000004602 germ cell Anatomy 0.000 claims description 10
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 9
- 239000000032 diagnostic agent Substances 0.000 claims description 9
- 229940039227 diagnostic agent Drugs 0.000 claims description 9
- 210000000822 natural killer cell Anatomy 0.000 claims description 9
- 230000001225 therapeutic effect Effects 0.000 claims description 9
- 102000004127 Cytokines Human genes 0.000 claims description 8
- 108090000695 Cytokines Proteins 0.000 claims description 8
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 8
- 239000012190 activator Substances 0.000 claims description 8
- 238000007792 addition Methods 0.000 claims description 8
- 229940124675 anti-cancer drug Drugs 0.000 claims description 8
- 239000012216 imaging agent Substances 0.000 claims description 8
- 210000002865 immune cell Anatomy 0.000 claims description 8
- 239000003207 proteasome inhibitor Substances 0.000 claims description 8
- 150000003384 small molecules Chemical class 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 229960005486 vaccine Drugs 0.000 claims description 8
- 206010009944 Colon cancer Diseases 0.000 claims description 7
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 229940125697 hormonal agent Drugs 0.000 claims description 7
- 201000002528 pancreatic cancer Diseases 0.000 claims description 7
- 206010005003 Bladder cancer Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 6
- 208000032612 Glial tumor Diseases 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 6
- 206010038389 Renal cancer Diseases 0.000 claims description 6
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 6
- 101150117115 V gene Proteins 0.000 claims description 6
- 238000012217 deletion Methods 0.000 claims description 6
- 230000037430 deletion Effects 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 6
- 201000010982 kidney cancer Diseases 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 6
- 201000007270 liver cancer Diseases 0.000 claims description 6
- 208000014018 liver neoplasm Diseases 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- -1 oncolytic drugs Substances 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 6
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 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 claims description 5
- 201000004101 esophageal cancer Diseases 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 238000002648 combination therapy Methods 0.000 claims description 4
- 238000003745 diagnosis Methods 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 241000588724 Escherichia coli Species 0.000 claims description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 3
- 230000000139 costimulatory effect Effects 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 230000001177 retroviral effect Effects 0.000 claims description 3
- 101100450694 Arabidopsis thaliana HFR1 gene Proteins 0.000 claims description 2
- 101001047617 Homo sapiens Immunoglobulin kappa variable 3-11 Proteins 0.000 claims description 2
- 102100022955 Immunoglobulin kappa variable 3-11 Human genes 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 50
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 abstract description 22
- 230000012202 endocytosis Effects 0.000 abstract description 4
- 230000009036 growth inhibition Effects 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 229950007157 zolbetuximab Drugs 0.000 description 47
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 38
- 102000004169 proteins and genes Human genes 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 26
- 150000001413 amino acids Chemical class 0.000 description 24
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 20
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 231100000673 dose–response relationship Toxicity 0.000 description 16
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
- 239000006285 cell suspension Substances 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 108010059074 monomethylauristatin F Proteins 0.000 description 12
- 101150087140 nudC gene Proteins 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 238000010790 dilution Methods 0.000 description 10
- 239000012895 dilution Substances 0.000 description 10
- 230000002121 endocytic effect Effects 0.000 description 10
- 238000011534 incubation Methods 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 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 9
- 239000012980 RPMI-1640 medium Substances 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 102000002029 Claudin Human genes 0.000 description 8
- 108050009302 Claudin Proteins 0.000 description 8
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000013642 negative control Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000013543 active substance Substances 0.000 description 7
- 239000000562 conjugate Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 238000012054 celltiter-glo Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 102100030453 Hemoglobin subunit mu Human genes 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000004020 luminiscence type Methods 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 230000002269 spontaneous effect Effects 0.000 description 5
- QWPXBEHQFHACTK-KZVYIGENSA-N (10e,12e)-86-chloro-12,14,4-trihydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-15,16-dihydro-14h-7-aza-1(6,4)-oxazina-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-6-one Chemical compound CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-KZVYIGENSA-N 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 241000713666 Lentivirus Species 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
- 102000025171 antigen binding proteins Human genes 0.000 description 4
- 108091000831 antigen binding proteins Proteins 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000009137 competitive binding Effects 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 239000000834 fixative Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 230000001394 metastastic effect Effects 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 108010093470 monomethyl auristatin E Proteins 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 230000004481 post-translational protein modification Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- QWPXBEHQFHACTK-UHFFFAOYSA-N Maytansinol Natural products CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-UHFFFAOYSA-N 0.000 description 3
- SCJNCDSAIRBRIA-DOFZRALJSA-N arachidonyl-2'-chloroethylamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCCl SCJNCDSAIRBRIA-DOFZRALJSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 238000012200 cell viability kit Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940044683 chemotherapy drug Drugs 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 101150058725 ecl1 gene Proteins 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000009422 growth inhibiting effect Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000011426 transformation method Methods 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 102100040835 Claudin-18 Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000749329 Homo sapiens Claudin-18 Proteins 0.000 description 2
- 102000014748 Junctional Adhesion Molecules Human genes 0.000 description 2
- 108010064064 Junctional Adhesion Molecules Proteins 0.000 description 2
- 241001441512 Maytenus serrata Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 230000004988 N-glycosylation Effects 0.000 description 2
- 102000003940 Occludin Human genes 0.000 description 2
- 108090000304 Occludin Proteins 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 241000712907 Retroviridae Species 0.000 description 2
- 101100225046 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ecl2 gene Proteins 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 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 2
- 238000012215 gene cloning Methods 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 230000002584 immunomodulator Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012521 purified sample Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 102220269348 rs61747367 Human genes 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000036964 tight binding Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 230000005909 tumor killing Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 102100023990 60S ribosomal protein L17 Human genes 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 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
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000002038 Claudin-18 Human genes 0.000 description 1
- 108050009324 Claudin-18 Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- JHKFWJUVTLNOJZ-UHFFFAOYSA-N Dolabellin Natural products COC(=O)C1=CSC(C(OC(=O)C(C)C(CCCC(C)(Cl)Cl)OC(=O)C=2N=C(SC=2)C(O)CO)C(C)C)=N1 JHKFWJUVTLNOJZ-UHFFFAOYSA-N 0.000 description 1
- OFDNQWIFNXBECV-UHFFFAOYSA-N Dolastatin 10 Natural products CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-UHFFFAOYSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061968 Gastric neoplasm Diseases 0.000 description 1
- 206010062878 Gastrooesophageal cancer Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- 229930126263 Maytansine Natural products 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010063916 Metastatic gastric cancer Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229940123066 Polymerase inhibitor Drugs 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102000000591 Tight Junction Proteins Human genes 0.000 description 1
- 108010002321 Tight Junction Proteins Proteins 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- JHKFWJUVTLNOJZ-ZSGPHXLJSA-N [(2r,3s)-7,7-dichloro-1-[(1s)-1-(4-methoxycarbonyl-1,3-thiazol-2-yl)-2-methylpropoxy]-2-methyl-1-oxooctan-3-yl] 2-[(1r)-1,2-dihydroxyethyl]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC([C@@H](OC(=O)[C@H](C)[C@H](CCCC(C)(Cl)Cl)OC(=O)C=2N=C(SC=2)[C@H](O)CO)C(C)C)=N1 JHKFWJUVTLNOJZ-ZSGPHXLJSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229960003982 apatinib Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 108010044540 auristatin Proteins 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 description 1
- 108010045524 dolastatin 10 Proteins 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 201000006974 gastroesophageal cancer Diseases 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000012516 mab select resin Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- WPEWQEMJFLWMLV-UHFFFAOYSA-N n-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C=1C=CN=C(NCC=2C=CN=CC=2)C=1C(=O)NC(C=C1)=CC=C1C1(C#N)CCCC1 WPEWQEMJFLWMLV-UHFFFAOYSA-N 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 208000025402 neoplasm of esophagus Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000003725 paracellular diffusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229960001796 sunitinib Drugs 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
- 239000013595 supernatant sample Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 108020005087 unfolded proteins Proteins 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- 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
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
-
- 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
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C07K2317/50—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
-
- 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
- C07K2317/50—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
- C07K2317/567—Framework region [FR]
-
- 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
- C07K2317/71—Decreased 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
- C07K2317/72—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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Wood Science & Technology (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
Abstract
Description
Claims (24)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2019109413163 | 2019-09-30 | ||
CN201910941316.3A CN112707965A (zh) | 2019-09-30 | 2019-09-30 | 靶向cldn18.2的抗体及其制备方法和应用 |
PCT/CN2020/118650 WO2021063336A1 (zh) | 2019-09-30 | 2020-09-29 | 靶向cldn18.2的抗体及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114502592A true CN114502592A (zh) | 2022-05-13 |
CN114502592B CN114502592B (zh) | 2024-10-01 |
Family
ID=75336698
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910941316.3A Pending CN112707965A (zh) | 2019-09-30 | 2019-09-30 | 靶向cldn18.2的抗体及其制备方法和应用 |
CN202080068747.4A Active CN114502592B (zh) | 2019-09-30 | 2020-09-29 | 靶向cldn18.2的抗体及其制备方法和应用 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910941316.3A Pending CN112707965A (zh) | 2019-09-30 | 2019-09-30 | 靶向cldn18.2的抗体及其制备方法和应用 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20220332814A1 (zh) |
EP (1) | EP4039706A4 (zh) |
JP (1) | JP7461469B2 (zh) |
KR (1) | KR20220075396A (zh) |
CN (2) | CN112707965A (zh) |
TW (1) | TWI784322B (zh) |
WO (1) | WO2021063336A1 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115947851A (zh) * | 2022-12-19 | 2023-04-11 | 华润生物医药有限公司 | 结合cldn18.2的抗体及其用途 |
CN115960229A (zh) * | 2022-09-28 | 2023-04-14 | 华润生物医药有限公司 | 一种cldn18.2抗体及其应用 |
CN115969997A (zh) * | 2022-12-19 | 2023-04-18 | 华润生物医药有限公司 | 一种靶向cldn18.2的抗体药物偶联物及其应用 |
CN116003603A (zh) * | 2022-12-19 | 2023-04-25 | 华润生物医药有限公司 | 一种cldn18.2抗体及其应用 |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113416260B (zh) * | 2021-04-14 | 2022-02-01 | 南京凯地医疗技术有限公司 | 靶向Claudin18.2的特异性嵌合抗原受体细胞及其制备方法和应用 |
WO2022268200A1 (zh) * | 2021-06-25 | 2022-12-29 | 信达生物制药(苏州)有限公司 | 针对密蛋白18.2的抗体及其用途 |
CN115611983A (zh) * | 2021-07-14 | 2023-01-17 | 三优生物医药(上海)有限公司 | Cldn18.2结合分子及其用途 |
EP4393515A1 (en) * | 2021-08-26 | 2024-07-03 | Shanghai Junshi Biosciences Co., Ltd. | Anti-cldn-18.2 antibody-drug conjugate and use thereof |
CN115991784A (zh) * | 2021-10-19 | 2023-04-21 | 宝船生物医药科技(上海)有限公司 | 抗cd47-cldn18.2双特异性抗体及其用途 |
CN116102649A (zh) * | 2021-11-11 | 2023-05-12 | 上海生物制品研究所有限责任公司 | 抗cldn18.2单克隆抗体及其应用 |
KR20240133715A (ko) * | 2021-12-17 | 2024-09-04 | 포트비타 바이오로직스 (싱가포르) 피티이. 리미티드 | Claudin18.2를 표적으로 하는 항체-약물 접합체 |
CN114316043B (zh) * | 2021-12-28 | 2022-09-20 | 三优生物医药(上海)有限公司 | 一种TGFβ1抗原结合分子及其应用 |
CN117500529A (zh) * | 2022-05-31 | 2024-02-02 | 石药集团巨石生物制药有限公司 | 重组抗人cldn18.2单克隆抗体-mmae偶联药物的药物组合物 |
WO2024131683A1 (zh) * | 2022-12-19 | 2024-06-27 | 华润生物医药有限公司 | 结合cldn18.2的抗体和抗体药物偶联物及其用途 |
CN116082523B (zh) * | 2022-12-30 | 2023-10-13 | 邦恩泰(山东)生物医药科技集团股份有限公司 | 一种靶向Claudin18.2的嵌合抗原受体及其应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1948693A1 (en) * | 2005-11-24 | 2008-07-30 | Ganymed Pharmaceuticals AG | Monoclonal antibodies against claudin-18 for treatment of cancer |
EP3170842A1 (en) * | 2014-07-17 | 2017-05-24 | Carsgen Therapeutics Limited | Immunologic effector cell of targeted cld18a2, and preparation method and use thereof |
US10421817B1 (en) * | 2019-01-17 | 2019-09-24 | Beijing Mabworks Biotech Co., Ltd. | Antibodies binding human Claudin 18.2 and uses thereof |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3896111A (en) | 1973-02-20 | 1975-07-22 | Research Corp | Ansa macrolides |
US4151042A (en) | 1977-03-31 | 1979-04-24 | Takeda Chemical Industries, Ltd. | Method for producing maytansinol and its derivatives |
US7750116B1 (en) | 2006-02-18 | 2010-07-06 | Seattle Genetics, Inc. | Antibody drug conjugate metabolites |
WO2013174404A1 (en) * | 2012-05-23 | 2013-11-28 | Ganymed Pharmaceuticals Ag | Combination therapy involving antibodies against claudin 18.2 for treatment of cancer |
WO2014146672A1 (en) | 2013-03-18 | 2014-09-25 | Ganymed Pharmaceuticals Ag | Therapy involving antibodies against claudin 18.2 for treatment of cancer |
ES2699753T3 (es) * | 2014-01-29 | 2019-02-12 | Biontech Ag | Mimótopos peptídicos de claudina 18.2 y sus usos |
WO2016165762A1 (en) | 2015-04-15 | 2016-10-20 | Ganymed Pharmaceuticals Ag | Drug conjugates comprising antibodies against claudin 18.2 |
EP3762031A4 (en) | 2018-03-08 | 2021-12-22 | Phanes Therapeutics, Inc. | ANTI-CLAUDINE ANTIBODIES 18.2 AND THEIR USES |
CA3087423A1 (en) * | 2018-03-14 | 2019-09-19 | Beijing Xuanyi Pharmasciences Co., Ltd. | Anti-claudin 18.2 antibodies |
-
2019
- 2019-09-30 CN CN201910941316.3A patent/CN112707965A/zh active Pending
-
2020
- 2020-09-29 EP EP20872423.7A patent/EP4039706A4/en active Pending
- 2020-09-29 WO PCT/CN2020/118650 patent/WO2021063336A1/zh unknown
- 2020-09-29 KR KR1020227014720A patent/KR20220075396A/ko active Search and Examination
- 2020-09-29 US US17/764,338 patent/US20220332814A1/en active Pending
- 2020-09-29 CN CN202080068747.4A patent/CN114502592B/zh active Active
- 2020-09-29 TW TW109133811A patent/TWI784322B/zh active
- 2020-09-29 JP JP2022520345A patent/JP7461469B2/ja active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1948693A1 (en) * | 2005-11-24 | 2008-07-30 | Ganymed Pharmaceuticals AG | Monoclonal antibodies against claudin-18 for treatment of cancer |
EP3170842A1 (en) * | 2014-07-17 | 2017-05-24 | Carsgen Therapeutics Limited | Immunologic effector cell of targeted cld18a2, and preparation method and use thereof |
US10421817B1 (en) * | 2019-01-17 | 2019-09-24 | Beijing Mabworks Biotech Co., Ltd. | Antibodies binding human Claudin 18.2 and uses thereof |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115960229A (zh) * | 2022-09-28 | 2023-04-14 | 华润生物医药有限公司 | 一种cldn18.2抗体及其应用 |
CN115960229B (zh) * | 2022-09-28 | 2024-02-09 | 华润生物医药有限公司 | 一种cldn18.2抗体及其应用 |
CN115947851A (zh) * | 2022-12-19 | 2023-04-11 | 华润生物医药有限公司 | 结合cldn18.2的抗体及其用途 |
CN115969997A (zh) * | 2022-12-19 | 2023-04-18 | 华润生物医药有限公司 | 一种靶向cldn18.2的抗体药物偶联物及其应用 |
CN116003603A (zh) * | 2022-12-19 | 2023-04-25 | 华润生物医药有限公司 | 一种cldn18.2抗体及其应用 |
CN115969997B (zh) * | 2022-12-19 | 2024-02-13 | 华润生物医药有限公司 | 一种靶向cldn18.2的抗体药物偶联物及其应用 |
CN115947851B (zh) * | 2022-12-19 | 2024-02-13 | 华润生物医药有限公司 | 结合cldn18.2的抗体及其用途 |
CN116003603B (zh) * | 2022-12-19 | 2024-07-12 | 华润生物医药有限公司 | 一种cldn18.2抗体及其应用 |
Also Published As
Publication number | Publication date |
---|---|
WO2021063336A1 (zh) | 2021-04-08 |
EP4039706A4 (en) | 2023-03-01 |
TWI784322B (zh) | 2022-11-21 |
EP4039706A1 (en) | 2022-08-10 |
JP2022550952A (ja) | 2022-12-06 |
US20220332814A1 (en) | 2022-10-20 |
JP7461469B2 (ja) | 2024-04-03 |
KR20220075396A (ko) | 2022-06-08 |
CN114502592B (zh) | 2024-10-01 |
CN112707965A (zh) | 2021-04-27 |
TW202126695A (zh) | 2021-07-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114502592B (zh) | 靶向cldn18.2的抗体及其制备方法和应用 | |
US20210230272A1 (en) | Antibody targeting cldn18.2, bispecific antibody, adc, and car, and applications thereof | |
JP2021531826A (ja) | 栄養膜細胞表面抗原2(trop2)に対する特異的な抗体 | |
CN113166246A (zh) | 一种抗体及其用途 | |
US20220041748A1 (en) | Antibodies specific to muc18 | |
US20220041749A1 (en) | Antibodies specific to muc18 | |
CN116323946A (zh) | 靶向ror1的抗体或其抗原结合片段及制备方法和应用 | |
EP4208259A2 (en) | Nectin-4 antibodies and uses thereof | |
EP3821006A2 (en) | Antibodies specific to folate receptor alpha | |
WO2021169982A1 (zh) | 靶向EpCAM的抗体及其制备和应用 | |
WO2023016348A1 (en) | Cldn18.2-targeting antibody, bispecific antibody and use thereof | |
TWI855014B (zh) | Muc18特異性抗體 | |
WO2023138579A1 (zh) | 抗b7-h7抗体或其抗原结合片段及制备方法和应用 | |
TW202246323A (zh) | 抗claudin—6之抗體及其用途 | |
CN114685658A (zh) | Ox40的靶向抗体及其制备方法和应用 |
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 | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40066347 Country of ref document: HK |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: CORR Ref document number: 40066347 Country of ref document: HK Free format text: CORRECTED DATA OF SECTION 20 12.08.2022: (54) CLDN18.2-TARGETING ANTIBODY, PREPARATION METHOD THEREOF, AND USE THEREOF |
|
CB02 | Change of applicant information |
Address after: 215000 unit 202, A3 / F, 218 Xinghu street, Suzhou Industrial Park, Jiangsu Province Applicant after: Nuona Biological (Suzhou) Co.,Ltd. Address before: 215000 unit 202, A3 / F, 218 Xinghu street, Suzhou Industrial Park, Jiangsu Province Applicant before: Heping Pharmaceutical (Suzhou) Co.,Ltd. |
|
CB02 | Change of applicant information | ||
GR01 | Patent grant | ||
GR01 | Patent grant |