CN103172741A - 新型全人源抗体 - Google Patents
新型全人源抗体 Download PDFInfo
- Publication number
- CN103172741A CN103172741A CN2011104303813A CN201110430381A CN103172741A CN 103172741 A CN103172741 A CN 103172741A CN 2011104303813 A CN2011104303813 A CN 2011104303813A CN 201110430381 A CN201110430381 A CN 201110430381A CN 103172741 A CN103172741 A CN 103172741A
- Authority
- CN
- China
- Prior art keywords
- antibody
- egfr
- human antibody
- sequence
- seq
- 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
- 238000000034 method Methods 0.000 claims abstract description 22
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 40
- 239000012634 fragment Substances 0.000 claims description 12
- 230000014509 gene expression Effects 0.000 claims description 12
- 230000001413 cellular effect Effects 0.000 claims description 8
- 230000003013 cytotoxicity Effects 0.000 claims description 7
- 231100000135 cytotoxicity Toxicity 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 7
- 108020004414 DNA Proteins 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 241000700605 Viruses Species 0.000 claims description 5
- 238000001890 transfection Methods 0.000 claims description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- 238000013461 design Methods 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000013613 expression plasmid Substances 0.000 claims description 2
- 210000004962 mammalian cell Anatomy 0.000 claims description 2
- 230000002103 transcriptional effect Effects 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 102000053602 DNA Human genes 0.000 claims 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 abstract description 3
- 230000000118 anti-neoplastic effect Effects 0.000 abstract 1
- 229960001972 panitumumab Drugs 0.000 abstract 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 87
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 87
- 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 87
- 230000000694 effects Effects 0.000 description 23
- 229940082789 erbitux Drugs 0.000 description 18
- 230000026731 phosphorylation Effects 0.000 description 10
- 238000006366 phosphorylation reaction Methods 0.000 description 10
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 8
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 8
- 229960005395 cetuximab Drugs 0.000 description 8
- 102000001301 EGF receptor Human genes 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 229940125644 antibody drug Drugs 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 3
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 3
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 238000013016 damping Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 3
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000005374 membrane filtration Methods 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000009967 tasteless effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 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
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 101100015729 Drosophila melanogaster drk gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 108091082332 JAK family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 241001417495 Serranidae Species 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229940021171 curative drug Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 101150098203 grb2 gene Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000012516 mab select resin Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000011242 molecular targeted therapy Methods 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 210000004493 neutrocyte Anatomy 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000013326 plasmid cotransfection Methods 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000001855 preneoplastic effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- -1 small molecules quinolines Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Abstract
Description
Claims (11)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110430381.3A CN103172741B (zh) | 2011-12-20 | 2011-12-20 | 全人源抗egfr抗体 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110430381.3A CN103172741B (zh) | 2011-12-20 | 2011-12-20 | 全人源抗egfr抗体 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103172741A true CN103172741A (zh) | 2013-06-26 |
CN103172741B CN103172741B (zh) | 2018-04-27 |
Family
ID=48632982
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201110430381.3A Expired - Fee Related CN103172741B (zh) | 2011-12-20 | 2011-12-20 | 全人源抗egfr抗体 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103172741B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104910275A (zh) * | 2014-12-04 | 2015-09-16 | 上海张江生物技术有限公司 | 一种新型抗表皮生长因子受体抗体、其制备方法及用途 |
US20160017045A1 (en) * | 2013-04-07 | 2016-01-21 | Bioex Therapeutics Inc. | Epidermal growth factor receptor antibody |
CN105669867A (zh) * | 2014-11-21 | 2016-06-15 | 上海中信国健药业股份有限公司 | 抗gitr/ctla-4双特异性抗体及其制备方法和用途 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1610695A (zh) * | 2001-06-13 | 2005-04-27 | 根马布股份公司 | 表皮生长因子受体(egfr)的人单克隆抗体 |
CN1930187A (zh) * | 2003-06-27 | 2007-03-14 | 艾伯吉尼斯公司 | 针对表皮生长因子受体的缺失突变体的抗体及其使用 |
EP0979246B1 (en) * | 1997-05-05 | 2007-07-11 | Amgen Fremont Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
-
2011
- 2011-12-20 CN CN201110430381.3A patent/CN103172741B/zh not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0979246B1 (en) * | 1997-05-05 | 2007-07-11 | Amgen Fremont Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
CN1610695A (zh) * | 2001-06-13 | 2005-04-27 | 根马布股份公司 | 表皮生长因子受体(egfr)的人单克隆抗体 |
CN1930187A (zh) * | 2003-06-27 | 2007-03-14 | 艾伯吉尼斯公司 | 针对表皮生长因子受体的缺失突变体的抗体及其使用 |
Non-Patent Citations (3)
Title |
---|
CHARLOTTE MAGDELAINE-BEUZELIN等: "Structure–function relationships of the variable domains of monoclonal antibodies approved for cancer treatment", 《CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY》 * |
XIAO-DONG YANG等: "Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody,for cancer therapy", 《CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY》 * |
ZENON STEPLEWSKI等: "Biological activity of human-mouse IgGl, IgG2, IgG3, and IgG4 chimeric monoclonal antibodies with antitumor specificity", 《PROC.NATL.ACAD.SCI.》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160017045A1 (en) * | 2013-04-07 | 2016-01-21 | Bioex Therapeutics Inc. | Epidermal growth factor receptor antibody |
US9644031B2 (en) * | 2013-04-07 | 2017-05-09 | Genrix (Shanghai) Biopharmacertical Co., Ltd. | Epidermal growth factor receptor antibody |
CN105669867A (zh) * | 2014-11-21 | 2016-06-15 | 上海中信国健药业股份有限公司 | 抗gitr/ctla-4双特异性抗体及其制备方法和用途 |
CN104910275A (zh) * | 2014-12-04 | 2015-09-16 | 上海张江生物技术有限公司 | 一种新型抗表皮生长因子受体抗体、其制备方法及用途 |
Also Published As
Publication number | Publication date |
---|---|
CN103172741B (zh) | 2018-04-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6827583B2 (ja) | Dll3及びcd3に結合する二重特異性抗体構築物 | |
JP7283806B2 (ja) | 抗pd-l1/vegf二機能性抗体およびその用途 | |
JP2021532170A (ja) | 三重特異性アンタゴニスト | |
EP4261231A1 (en) | Bispecific antibody and application thereof | |
KR20180031728A (ko) | 다가 및 다중특이적 gitr 결합 융합 단백질 | |
CN109912717B (zh) | 结合cd40的抗体及其用途 | |
TW201444872A (zh) | 抗C-MET串聯Fc雙特異性抗體 | |
ES2699584T3 (es) | Anticuerpos multifuncionales que se unen a EGFR y MET | |
AU2010229705A1 (en) | Compositions and methods for using multispecific-binding proteins comprising an antibody-receptor combination | |
WO2021219127A1 (zh) | 一种靶向her2和pd-1的双特异性抗体及其应用 | |
WO2017048699A2 (en) | Highly potent monoclonal antibodies to angiogenic factors | |
JP2024504124A (ja) | 新規の抗グレムリン1抗体 | |
WO2019114793A1 (zh) | 一种egfr抗体及其制备方法和应用 | |
US9644031B2 (en) | Epidermal growth factor receptor antibody | |
CN103172741A (zh) | 新型全人源抗体 | |
WO2021244553A1 (zh) | 一种抗pd-l1和egfr的四价双特异性抗体 | |
US9464136B2 (en) | Antibody-based constructs directed against tyrosine kinase receptors | |
CN114316045A (zh) | 抗pd-l1抗体及其用途 | |
US20220153869A1 (en) | Shielded and homing bispecific antibody that simultaneously inhibits angiogenic pathway targets and her2 family proteins and uses thereof | |
CN117510641A (zh) | 靶向cd112r和tigit的双特异性抗体及其用途 | |
KR101631646B1 (ko) | VEGFR-2 및 c-Met에 대하여 결합성을 갖는 이중표적항체 | |
CA3232216A1 (en) | Anti-egfr antibodies, anti-cmet antibodies, anti-vegf antibodies, multispecific antibodies, and uses thereof | |
TW202328186A (zh) | 抗her2抗體及其使用方法 | |
CN116462765A (zh) | 抗cd3和抗cd20双特异性抗体及其用途 | |
CN112867733A (zh) | 抗cd137抗体及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
ASS | Succession or assignment of patent right |
Owner name: GENRIX (SHANGHAI) BIOPHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: YONGZHUO BOJI (SHANGHAI) BIOMEDICAL TECHNOLOGY CO., LTD. Effective date: 20150116 Owner name: YONGZHUO BOJI (SHANGHAI) BIOMEDICAL TECHNOLOGY CO. Free format text: FORMER OWNER: SHANGHAI ZHONGHE MEDICAL TECHNOLOGY CO., LTD. Effective date: 20150116 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20150116 Address after: 201210 Shanghai Zhangjiang High Tech Park of Pudong New Area Cailun Road No. 333 building A room 703 Applicant after: GENRIX (SHANGHAI) BIOPHARMACEUTICAL Co.,Ltd. Applicant after: BIOEX THERAPEUTICS Inc. Address before: 201210 Shanghai Zhangjiang High Tech Park of Pudong Cailun Road No. 333 building A room 703 Applicant before: BIOEX THERAPEUTICS Inc. Applicant before: SHANGHAI UNION BIOPHARM Co.,Ltd. |
|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20191111 Address after: 201210 Shanghai Zhangjiang High Tech Park of Pudong New Area Cailun Road No. 333 building A room 703 Co-patentee after: BIOEX THERAPEUTICS Inc. Patentee after: GENRIX (SHANGHAI) BIOPHARMACEUTICAL Co.,Ltd. Co-patentee after: CHONGQING GENRIX BIOPHARMACEUTICAL Co.,Ltd. Address before: 201210 Shanghai Zhangjiang High Tech Park of Pudong New Area Cailun Road No. 333 building A room 703 Co-patentee before: BIOEX THERAPEUTICS Inc. Patentee before: GENRIX (SHANGHAI) BIOPHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20221129 Address after: 201210 Room 703, Block A, No. 333, Cailun Road, Zhangjiang Hi Tech Park, Pudong New Area, Shanghai Patentee after: BIOEX THERAPEUTICS Inc. Address before: 201210 Room 703, Block A, No. 333, Cailun Road, Zhangjiang Hi Tech Park, Pudong New Area, Shanghai Patentee before: GENRIX (SHANGHAI) BIOPHARMACEUTICAL Co.,Ltd. Patentee before: BIOEX THERAPEUTICS Inc. Patentee before: CHONGQING GENRIX BIOPHARMACEUTICAL Co.,Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180427 |