KR20150143458A - 항-C-MET 탠덤 Fc 이중특이적 항체 - Google Patents
항-C-MET 탠덤 Fc 이중특이적 항체 Download PDFInfo
- Publication number
- KR20150143458A KR20150143458A KR1020157026790A KR20157026790A KR20150143458A KR 20150143458 A KR20150143458 A KR 20150143458A KR 1020157026790 A KR1020157026790 A KR 1020157026790A KR 20157026790 A KR20157026790 A KR 20157026790A KR 20150143458 A KR20150143458 A KR 20150143458A
- Authority
- KR
- South Korea
- Prior art keywords
- seq
- domain
- tfcba
- sequence
- tfc
- 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.)
- Withdrawn
Links
- 230000027455 binding Effects 0.000 claims abstract description 349
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 58
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 40
- 229920001184 polypeptide Polymers 0.000 claims abstract description 38
- 101150084967 EPCAM gene Proteins 0.000 claims abstract description 25
- 239000000539 dimer Substances 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 317
- 108090000623 proteins and genes Proteins 0.000 claims description 153
- 102000004169 proteins and genes Human genes 0.000 claims description 122
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 106
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims description 103
- 206010028980 Neoplasm Diseases 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 64
- 150000007523 nucleic acids Chemical class 0.000 claims description 58
- 102000039446 nucleic acids Human genes 0.000 claims description 57
- 108020004707 nucleic acids Proteins 0.000 claims description 57
- 210000004899 c-terminal region Anatomy 0.000 claims description 34
- 230000035772 mutation Effects 0.000 claims description 33
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
- 201000011510 cancer Diseases 0.000 claims description 24
- 102000012804 EPCAM Human genes 0.000 claims description 21
- 101150057140 TACSTD1 gene Proteins 0.000 claims description 21
- 239000013598 vector Substances 0.000 claims description 17
- 230000004663 cell proliferation Effects 0.000 claims description 14
- 230000037396 body weight Effects 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 210000004881 tumor cell Anatomy 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 230000004614 tumor growth Effects 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 6
- 230000035755 proliferation Effects 0.000 claims description 6
- 238000001802 infusion Methods 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims description 2
- 230000011664 signaling Effects 0.000 abstract description 22
- 108010001857 Cell Surface Receptors Proteins 0.000 abstract description 9
- 102000006240 membrane receptors Human genes 0.000 abstract 2
- 235000018102 proteins Nutrition 0.000 description 112
- 238000006467 substitution reaction Methods 0.000 description 95
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 77
- 239000002953 phosphate buffered saline Substances 0.000 description 77
- 230000004048 modification Effects 0.000 description 69
- 238000012986 modification Methods 0.000 description 69
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 61
- 239000002773 nucleotide Substances 0.000 description 61
- 125000003729 nucleotide group Chemical group 0.000 description 61
- 150000001413 amino acids Chemical class 0.000 description 60
- 239000000427 antigen Substances 0.000 description 57
- 102000036639 antigens Human genes 0.000 description 57
- 108091007433 antigens Proteins 0.000 description 57
- 238000007792 addition Methods 0.000 description 56
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 52
- 238000012217 deletion Methods 0.000 description 52
- 230000037430 deletion Effects 0.000 description 52
- 235000001014 amino acid Nutrition 0.000 description 50
- 230000004071 biological effect Effects 0.000 description 50
- 102000005962 receptors Human genes 0.000 description 50
- 108020003175 receptors Proteins 0.000 description 50
- 230000014509 gene expression Effects 0.000 description 49
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 45
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 45
- 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 43
- 239000003446 ligand Substances 0.000 description 42
- 230000026731 phosphorylation Effects 0.000 description 39
- 238000006366 phosphorylation reaction Methods 0.000 description 39
- 239000011324 bead Substances 0.000 description 38
- 239000002609 medium Substances 0.000 description 36
- 235000018417 cysteine Nutrition 0.000 description 35
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- 230000000694 effects Effects 0.000 description 30
- 230000005764 inhibitory process Effects 0.000 description 29
- 230000001965 increasing effect Effects 0.000 description 28
- 239000000178 monomer Substances 0.000 description 28
- 230000006870 function Effects 0.000 description 27
- 238000001542 size-exclusion chromatography Methods 0.000 description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 25
- 230000001404 mediated effect Effects 0.000 description 25
- 239000000872 buffer Substances 0.000 description 24
- 229960005395 cetuximab Drugs 0.000 description 24
- 239000012636 effector Substances 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 24
- 238000002965 ELISA Methods 0.000 description 23
- 125000000539 amino acid group Chemical group 0.000 description 22
- -1 c-Met Proteins 0.000 description 22
- 238000005259 measurement Methods 0.000 description 22
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 21
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 21
- 238000005516 engineering process Methods 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 20
- 108091005461 Nucleic proteins Chemical group 0.000 description 20
- 108010076504 Protein Sorting Signals Proteins 0.000 description 20
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 20
- 229920001213 Polysorbate 20 Polymers 0.000 description 19
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 19
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 19
- 108060003951 Immunoglobulin Proteins 0.000 description 18
- 230000002494 anti-cea effect Effects 0.000 description 18
- 102000018358 immunoglobulin Human genes 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 17
- 238000011534 incubation Methods 0.000 description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 17
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 16
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 238000002022 differential scanning fluorescence spectroscopy Methods 0.000 description 16
- 239000006228 supernatant Substances 0.000 description 16
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 15
- 108010055196 EphA2 Receptor Proteins 0.000 description 15
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 15
- 238000010790 dilution Methods 0.000 description 15
- 239000012895 dilution Substances 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 14
- 230000001419 dependent effect Effects 0.000 description 14
- 238000010494 dissociation reaction Methods 0.000 description 14
- 230000005593 dissociations Effects 0.000 description 14
- 238000000684 flow cytometry Methods 0.000 description 14
- 230000019491 signal transduction Effects 0.000 description 14
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 13
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 13
- 230000008859 change Effects 0.000 description 13
- 239000000499 gel Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 13
- 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 13
- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 description 12
- 101001028831 Homo sapiens Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 12
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 12
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 12
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 12
- 239000004472 Lysine Substances 0.000 description 12
- 102100021435 Macrophage-stimulating protein receptor Human genes 0.000 description 12
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 12
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 12
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 12
- 230000000295 complement effect Effects 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 230000013595 glycosylation Effects 0.000 description 12
- 238000006206 glycosylation reaction Methods 0.000 description 12
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 12
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 12
- 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 11
- 102400001368 Epidermal growth factor Human genes 0.000 description 11
- 101800003838 Epidermal growth factor Proteins 0.000 description 11
- 101001106413 Homo sapiens Macrophage-stimulating protein receptor Proteins 0.000 description 11
- 102000003746 Insulin Receptor Human genes 0.000 description 11
- 108010001127 Insulin Receptor Proteins 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 11
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 11
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 11
- 238000006731 degradation reaction Methods 0.000 description 11
- 229940116977 epidermal growth factor Drugs 0.000 description 11
- 230000036252 glycation Effects 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 108091026890 Coding region Proteins 0.000 description 10
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 10
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 10
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 10
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 10
- 239000012979 RPMI medium Substances 0.000 description 10
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 10
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 239000006143 cell culture medium Substances 0.000 description 10
- 239000013592 cell lysate Substances 0.000 description 10
- 230000005754 cellular signaling Effects 0.000 description 10
- 239000013613 expression plasmid Substances 0.000 description 10
- 239000013604 expression vector Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000004365 Protease Substances 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 239000006166 lysate Substances 0.000 description 9
- 238000011002 quantification Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 102100032912 CD44 antigen Human genes 0.000 description 8
- 229930182816 L-glutamine Natural products 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 230000002708 enhancing effect Effects 0.000 description 8
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 8
- 238000003119 immunoblot Methods 0.000 description 8
- 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 7
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 7
- 102000000844 Cell Surface Receptors Human genes 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 108020004511 Recombinant DNA Proteins 0.000 description 7
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 235000019419 proteases Nutrition 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 6
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 6
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 6
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 description 6
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 6
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 6
- 229930182555 Penicillin Natural products 0.000 description 6
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 102000057308 human HGF Human genes 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000011580 nude mouse model Methods 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 229940049954 penicillin Drugs 0.000 description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 238000013207 serial dilution Methods 0.000 description 6
- 239000012679 serum free medium Substances 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 229960005322 streptomycin Drugs 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 5
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 5
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 5
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 5
- 108091092195 Intron Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 238000001042 affinity chromatography Methods 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 4
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 4
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 4
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 4
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 4
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 4
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 4
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 4
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 238000007405 data analysis Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 102000045108 human EGFR Human genes 0.000 description 4
- 101150026046 iga gene Proteins 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000012516 mab select resin Substances 0.000 description 4
- 230000008774 maternal effect Effects 0.000 description 4
- 230000027405 negative regulation of phosphorylation Effects 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- 229960001972 panitumumab Drugs 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 239000013014 purified material Substances 0.000 description 4
- 239000011535 reaction buffer Substances 0.000 description 4
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 4
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000003248 secreting effect Effects 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000003146 transient transfection Methods 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 3
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 238000000035 BCA protein assay Methods 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 3
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 3
- 101000807561 Homo sapiens Tyrosine-protein kinase receptor UFO Proteins 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 206010057249 Phagocytosis Diseases 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 3
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 239000012561 harvest cell culture fluid Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000008782 phagocytosis Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000012089 stop solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010257 thawing Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000004565 tumor cell growth Effects 0.000 description 3
- 230000003442 weekly effect Effects 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101100217502 Caenorhabditis elegans lgg-3 gene Proteins 0.000 description 2
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 description 2
- 108010073807 IgG Receptors Proteins 0.000 description 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 108090000526 Papain Proteins 0.000 description 2
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 2
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 2
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 229920002684 Sepharose Polymers 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
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 108010023337 axl receptor tyrosine kinase Proteins 0.000 description 2
- 239000003124 biologic agent Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- QGYLTGSHWIGJJD-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(F)=CC=C1C1=CSC2=NC=NC(NCC=3C=C4OCOC4=CC=3)=C12 QGYLTGSHWIGJJD-UHFFFAOYSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000011234 negative regulation of signal transduction Effects 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 229940055729 papain Drugs 0.000 description 2
- 235000019834 papain Nutrition 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 238000000751 protein extraction Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000011897 real-time detection Methods 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 108020001568 subdomains Proteins 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- 102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 description 1
- 101100454808 Caenorhabditis elegans lgg-2 gene Proteins 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 101710145225 Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 101800000155 Epiregulin Proteins 0.000 description 1
- 241001658031 Eris Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101100306202 Escherichia coli (strain K12) rpoB gene Proteins 0.000 description 1
- 108010021468 Fc gamma receptor IIA Proteins 0.000 description 1
- 108010021472 Fc gamma receptor IIB Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 101710182387 Fibroblast growth factor receptor 4 Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 1
- 101100501688 Homo sapiens ERBB2 gene Proteins 0.000 description 1
- 101100501692 Homo sapiens ERBB3 gene Proteins 0.000 description 1
- 101000938346 Homo sapiens Ephrin type-A receptor 2 Proteins 0.000 description 1
- 101000827746 Homo sapiens Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 101000827688 Homo sapiens Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 101000917148 Homo sapiens Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101001126417 Homo sapiens Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101710196759 Macrophage-stimulating protein receptor Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100230981 Mus musculus Hgf gene Proteins 0.000 description 1
- 101100306001 Mus musculus Mst1r gene Proteins 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
- 102000018967 Platelet-Derived Growth Factor beta Receptor Human genes 0.000 description 1
- 101710164680 Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100029837 Probetacellulin Human genes 0.000 description 1
- 102100025498 Proepiregulin Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108700003853 RON Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000013378 biophysical characterization Methods 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 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
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 108010011705 herstatin Proteins 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 102000051965 human ALK Human genes 0.000 description 1
- 102000048851 human CD44 Human genes 0.000 description 1
- 102000055705 human FGFR1 Human genes 0.000 description 1
- 102000055736 human FGFR2 Human genes 0.000 description 1
- 102000055709 human FGFR3 Human genes 0.000 description 1
- 102000055699 human FGFR4 Human genes 0.000 description 1
- 102000045648 human IGF1R Human genes 0.000 description 1
- 102000049215 human IGF2R Human genes 0.000 description 1
- 102000047882 human INSR Human genes 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000003367 kinetic assay Methods 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 102000049853 macrophage stimulating protein Human genes 0.000 description 1
- 108010053292 macrophage stimulating protein Proteins 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical group 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000011340 peptidyl-tyrosine autophosphorylation Effects 0.000 description 1
- 238000002135 phase contrast microscopy Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920001583 poly(oxyethylated polyols) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920001289 polyvinyl ether Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000035409 positive regulation of cell proliferation Effects 0.000 description 1
- 230000016833 positive regulation of signal transduction Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000032649 susceptibility to 9 autism Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—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
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361773788P | 2013-03-06 | 2013-03-06 | |
| US201361773764P | 2013-03-06 | 2013-03-06 | |
| US61/773,764 | 2013-03-06 | ||
| US61/773,788 | 2013-03-06 | ||
| PCT/US2014/021341 WO2014138449A1 (en) | 2013-03-06 | 2014-03-06 | Anti-c-met tandem fc bispecific antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20150143458A true KR20150143458A (ko) | 2015-12-23 |
Family
ID=50483485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020157026790A Withdrawn KR20150143458A (ko) | 2013-03-06 | 2014-03-06 | 항-C-MET 탠덤 Fc 이중특이적 항체 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US9458245B2 (enExample) |
| EP (1) | EP2964676A1 (enExample) |
| JP (1) | JP2016510755A (enExample) |
| KR (1) | KR20150143458A (enExample) |
| CN (1) | CN105705519A (enExample) |
| AU (1) | AU2014225661A1 (enExample) |
| BR (1) | BR112015021462A2 (enExample) |
| CA (1) | CA2902505A1 (enExample) |
| EA (1) | EA201591652A1 (enExample) |
| HK (1) | HK1220465A1 (enExample) |
| IL (1) | IL240594A0 (enExample) |
| MX (1) | MX2015011712A (enExample) |
| SG (1) | SG11201506451UA (enExample) |
| TW (1) | TW201444872A (enExample) |
| WO (1) | WO2014138449A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180101623A (ko) * | 2016-02-03 | 2018-09-12 | 암젠 리서치 (뮌헨) 게엠베하 | Psma 및 cd3 이중특이성 t 세포 맞물림 항체 작제물 |
| KR20180103084A (ko) * | 2016-02-03 | 2018-09-18 | 암젠 리서치 (뮌헨) 게엠베하 | Bcma 및 cd3 이중특이성 t 세포 맞물림 항체 작제물 |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對ｂｃｍａ之e3以及ｃｄ３的結合分子 |
| US9605084B2 (en) * | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| MX2015011712A (es) * | 2013-03-06 | 2016-04-04 | Merrimack Pharmaceuticals Inc | Anticerpos biespecificos fc en fila anti-c-met. |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| TWI689520B (zh) * | 2014-05-30 | 2020-04-01 | 漢霖生技股份有限公司 | 抗表皮生長因子受體（ｅｇｆｒ）抗體 |
| US20170306415A1 (en) * | 2014-10-01 | 2017-10-26 | Merrimack Phamaceuticals, Inc. | Predicting tumor responses to antibodies against hepatocyte growth factor (hgf) and/or its cognate receptor, c-met |
| KR101631646B1 (ko) * | 2014-10-16 | 2016-06-20 | 주식회사 파멥신 | VEGFR-2 및 c-Met에 대하여 결합성을 갖는 이중표적항체 |
| HRP20201756T8 (hr) * | 2014-11-21 | 2021-08-20 | Bristol-Myers Squibb Company | Antitijela koja sadrže modificirane regije teškog lanca |
| CN116333153A (zh) | 2014-11-26 | 2023-06-27 | 森科股份有限公司 | 结合cd3和肿瘤抗原的异二聚体抗体 |
| EA039859B1 (ru) * | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究（慕尼黑）公司 | Ｆｌｔ３及ｃｄ３抗體構築體 |
| TWI796283B (zh) | 2015-07-31 | 2023-03-21 | 德商安美基研究（慕尼黑）公司 | Ｍｓｌｎ及ｃｄ３抗體構築體 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究（慕尼黑）公司 | Egfrviii及cd3抗體構築體 |
| ES3020458T3 (en) * | 2015-08-07 | 2025-05-22 | Imaginab Inc | Antigen binding constructs to target molecules |
| WO2017070356A1 (en) * | 2015-10-23 | 2017-04-27 | Merrimack Pharmaceuticals, Inc. | DOSAGE AND ADMINISTRATION OF ANTI-c-MET, ANTI-EpCAM BISPECIFIC ANTIBODIES, USES THEREOF AND MENTHODS OF TREATMENT THEREWITH |
| HRP20220064T1 (hr) * | 2015-10-30 | 2022-04-15 | F. Hoffmann - La Roche Ag | Zglobno modificirani fragmenti protutijela i postupci za pripravu |
| CN106397598B (zh) * | 2016-02-23 | 2020-07-14 | 上海交通大学 | 多价多特异性抗体及免疫杂合蛋白的表达和制备方法 |
| TWI782930B (zh) | 2016-11-16 | 2022-11-11 | 美商再生元醫藥公司 | 抗ｍｅｔ抗體，結合ｍｅｔ之雙特異性抗原結合分子及其使用方法 |
| JP2020514301A (ja) * | 2017-01-06 | 2020-05-21 | モメンタ ファーマシューティカルズ インコーポレイテッド | 改変されたＦｃ抗原結合ドメイン構築体に関する組成物および方法 |
| US11266745B2 (en) | 2017-02-08 | 2022-03-08 | Imaginab, Inc. | Extension sequences for diabodies |
| US11701405B2 (en) * | 2018-01-26 | 2023-07-18 | City Of Hope | Chimeric antigen receptors and methods for reducing toxicity |
| MX2021000239A (es) | 2018-07-10 | 2021-03-25 | Regeneron Pharma | Modificacion de moleculas de union para minimizar interacciones preexistentes. |
| CN113164592A (zh) * | 2018-07-11 | 2021-07-23 | 动量制药公司 | 与工程化Fc-抗原结合结构域构建体有关的组合物和方法 |
| CR20210272A (es) * | 2018-11-26 | 2021-07-14 | Forty Seven Inc | Anticuerpos humanizados contra c-kit |
| WO2020113164A1 (en) * | 2018-11-30 | 2020-06-04 | Memorial Sloan Kettering Cancer Center | Heterodimeric tetravalency and specificity antibody compositions and uses thereof |
| KR20210134091A (ko) * | 2019-01-29 | 2021-11-08 | 그릿스톤 바이오, 인코포레이티드 | 다중특이적 결합 단백질 |
| KR20220063185A (ko) | 2019-09-16 | 2022-05-17 | 리제너론 파마슈티칼스 인코포레이티드 | 면역-pet 영상화를 위한 방사성 표지된 met 결합 단백질 |
| US20230265134A1 (en) * | 2019-09-30 | 2023-08-24 | Adimab, Llc | Ch1 domain variants engineered for preferential light chain pairing and multispecific antibodies comprising the same |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| EP4196163A4 (en) * | 2020-08-14 | 2024-08-28 | Chugai Seiyaku Kabushiki Kaisha | ONE-ARM ANTIGEN-BINDING MOLECULES AND THEIR USES |
| JP2024500354A (ja) * | 2020-12-10 | 2024-01-09 | インベンラ， インコーポレイテッド | ヘテロ二量体化のための直交変異 |
| CN112979827A (zh) * | 2021-03-04 | 2021-06-18 | 华东理工大学 | 一种抗EGFR scFv::FTH1/FTH1蛋白纳米粒子的应用 |
| JP2024511319A (ja) | 2021-03-09 | 2024-03-13 | ゼンコア インコーポレイテッド | Ｃｄ３及びｃｌｄｎ６に結合するヘテロ二量体抗体 |
| CN113234165B (zh) * | 2021-05-07 | 2023-02-28 | 暨南大学 | EpCAM的改造的结合蛋白及其应用 |
| CA3230934A1 (en) * | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-cmet antibodies and their uses |
| CN116554340A (zh) * | 2022-01-28 | 2023-08-08 | 江苏众红生物工程创药研究院有限公司 | 新型长效化和高活性且更安全的抗体构建体 |
| WO2024258870A2 (en) | 2023-06-12 | 2024-12-19 | Amgen Inc. | Lymphotoxin beta receptor agonist binding proteins |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
| US5892019A (en) | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
| US5468468A (en) | 1989-02-09 | 1995-11-21 | The United States Of America, As Represented By The Secretary Of The Department Of Health & Human Services | Method for making a monoclonal antibody, monoclonal antibodies to α PD |
| DE4205148A1 (de) | 1991-05-25 | 1993-01-21 | Boehringer Mannheim Gmbh | Monoklonale antikoerper gegen c-kit |
| EP0590058B1 (en) | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| US6696548B2 (en) | 1993-12-03 | 2004-02-24 | St. Jude Children's Research Hospital | Antibodies for recognition of alk protein tyrosine/kinase receptor |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5686292A (en) | 1995-06-02 | 1997-11-11 | Genentech, Inc. | Hepatocyte growth factor receptor antagonist antibodies and uses thereof |
| DE19638745C2 (de) | 1996-09-11 | 2001-05-10 | Schering Ag | Monoklonale Antikörper gegen die extrazelluläre Domäne des menschlichen VEGF - Rezeptorproteins (KDR) |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| US20020136721A1 (en) * | 1998-02-17 | 2002-09-26 | Schwall Ralph H. | Hepatocyte growth factor receptor antagonists and uses thereof |
| JP4334141B2 (ja) | 1998-04-20 | 2009-09-30 | グリカート バイオテクノロジー アクチェンゲゼルシャフト | 抗体依存性細胞傷害性を改善するための抗体のグリコシル化操作 |
| CA2369292C (en) | 1999-04-09 | 2010-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Method of modulating the activity of functional immune molecules |
| DE69934259T2 (de) | 1999-07-23 | 2007-05-31 | Glaxo Group Ltd., Greenford | Kombination von einem Anti-Ep-CAM-Antikörper mit einem chemotherapeutischen Mittel |
| US8071072B2 (en) | 1999-10-08 | 2011-12-06 | Hoffmann-La Roche Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| WO2001029246A1 (fr) | 1999-10-19 | 2001-04-26 | Kyowa Hakko Kogyo Co., Ltd. | Procede de production d'un polypeptide |
| JP4132547B2 (ja) | 2000-03-01 | 2008-08-13 | 富士フイルム株式会社 | 画像形成材料及びそれを用いた平版印刷版原版 |
| US20020119148A1 (en) | 2000-09-01 | 2002-08-29 | Gerritsen Mary E. | ErbB4 antagonists |
| US7101976B1 (en) | 2000-09-12 | 2006-09-05 | Purdue Research Foundation | EphA2 monoclonal antibodies and methods of making and using same |
| EA013563B1 (ru) | 2000-10-06 | 2010-06-30 | Киова Хакко Кирин Ко., Лтд. | Трансгенное животное, продуцирующее антитела с измененными углеводными цепями, способ получения антител и содержащее антитела лекарственное средство |
| AU2001294175A1 (en) | 2000-10-06 | 2002-04-22 | Kyowa Hakko Kogyo Co. Ltd. | Method of purifying antibody |
| AR032028A1 (es) | 2001-01-05 | 2003-10-22 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
| JP2005500018A (ja) | 2001-04-02 | 2005-01-06 | アイデック ファーマスーティカルズ コーポレイション | ＧｎＴＩＩＩと同時発現する組換え抗体 |
| DK1383785T3 (da) | 2001-05-03 | 2011-05-23 | Merck Patent Gmbh | Rekombinant tumorspecifikt antistof og anvendelse deraf |
| US6972324B2 (en) | 2001-05-18 | 2005-12-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Antibodies specific for CD44v6 |
| IL159177A0 (en) | 2001-06-20 | 2004-06-01 | Prochon Biotech Ltd | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| JP4355571B2 (ja) | 2001-07-19 | 2009-11-04 | ウニベルジテート チューリッヒ | ヒト可変ドメインの改変 |
| ATE430580T1 (de) | 2001-10-25 | 2009-05-15 | Genentech Inc | Glycoprotein-zusammensetzungen |
| ES2363765T3 (es) | 2002-01-31 | 2011-08-16 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Agonistas de fgfr. |
| CA2478169C (en) | 2002-03-04 | 2013-04-16 | Imclone Systems Incorporated | Human antibodies specific to kdr and uses thereof |
| EP1575509B1 (en) | 2002-05-10 | 2011-10-26 | Purdue Research Foundation | Epha2 agonistic monoclonal antibodies and methods of use thereof |
| US20080008713A1 (en) | 2002-06-28 | 2008-01-10 | Domantis Limited | Single domain antibodies against tnfr1 and methods of use therefor |
| US7232888B2 (en) | 2002-07-01 | 2007-06-19 | Massachusetts Institute Of Technology | Antibodies against tumor surface antigens |
| BRPI0407446A (pt) | 2003-02-13 | 2006-01-31 | Pharmacia Corp | Anticorpos para c-met para o tratamento de cânceres |
| ITMI20031127A1 (it) | 2003-06-05 | 2004-12-06 | Uni Degli Studi Del Piemont E Orientale Am | Anticorpi anti-hgf-r e loro uso |
| HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| NZ545776A (en) | 2003-08-22 | 2009-05-31 | Biogen Idec Inc | Improved antibodies having altered effector function and methods for making the same |
| CA2762955A1 (en) | 2003-10-16 | 2005-04-28 | Imclone Llc | Fibroblast growth factor receptor-1 inhibitors and methods of treatment thereof |
| WO2005063815A2 (en) | 2003-11-12 | 2005-07-14 | Biogen Idec Ma Inc. | Fcϝ receptor-binding polypeptide variants and methods related thereto |
| CA2545603A1 (en) | 2003-11-12 | 2005-05-26 | Biogen Idec Ma Inc. | Neonatal fc receptor (fcrn)-binding polypeptide variants, dimeric fc binding proteins and methods related thereto |
| WO2005063816A2 (en) | 2003-12-19 | 2005-07-14 | Genentech, Inc. | Monovalent antibody fragments useful as therapeutics |
| AU2005287404B2 (en) | 2004-07-22 | 2009-05-07 | Genentech, Inc. | HER2 antibody composition |
| US7476724B2 (en) | 2004-08-05 | 2009-01-13 | Genentech, Inc. | Humanized anti-cmet antibodies |
| MY146381A (en) | 2004-12-22 | 2012-08-15 | Amgen Inc | Compositions and methods relating relating to anti-igf-1 receptor antibodies |
| KR101363252B1 (ko) | 2005-02-04 | 2014-02-13 | 레이븐 바이오테크놀로지스, 인코퍼레이티드 | Ｅｐｈａ2에 결합하는 항체 및 그것의 사용방법 |
| EP2402374A1 (en) | 2005-02-07 | 2012-01-04 | GlycArt Biotechnology AG | Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof |
| EP1868648B1 (en) | 2005-03-25 | 2015-04-15 | Genentech, Inc. | Methods and compositions for modulating hyperstabilized c-met |
| MX2007013924A (es) | 2005-05-09 | 2008-01-28 | Glycart Biotechnology Ag | Moleculas que unen antigeno que tienen regiones fc modificadas y union alterada a receptores fc. |
| PT2100614E (pt) | 2005-06-17 | 2013-12-16 | Imclone Llc | Antagonistas de receptor para tratamento de cancro ósseo metastático |
| AR056857A1 (es) | 2005-12-30 | 2007-10-24 | U3 Pharma Ag | Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos |
| AU2007213920B2 (en) | 2006-02-09 | 2013-08-29 | Amgen Research (Munich) Gmbh | Treatment of metastatic breast cancer |
| US7951918B2 (en) | 2006-03-17 | 2011-05-31 | Biogen Idec Ma Inc. | Stabilized polypeptide compositions |
| TW200815470A (en) | 2006-03-30 | 2008-04-01 | Novartis Ag | Compositions and methods of use for antibodies of c-Met |
| TWI395754B (zh) | 2006-04-24 | 2013-05-11 | Amgen Inc | 人類化之ｃ-ｋｉｔ抗體 |
| RU2460540C2 (ru) | 2006-04-28 | 2012-09-10 | Деленекс Терапьютикс Аг | Антитела, связывающиеся с внеклеточным доменом тирозинкиназного рецептора (alk) |
| WO2008052796A1 (en) | 2006-11-03 | 2008-05-08 | U3 Pharma Gmbh | Fgfr4 antibodies |
| UY30776A1 (es) | 2006-12-21 | 2008-07-03 | Medarex Inc | Anticuerpos cd44 |
| HRP20131113T1 (hr) | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| EP1972637B1 (en) | 2007-03-19 | 2011-06-29 | Universität Stuttgart | huTNFR1 selective antagonists |
| BRPI0810374A2 (pt) | 2007-04-17 | 2014-10-29 | Imclone Llc | Inibidores específicos do pdgfrbeta |
| US20080260738A1 (en) * | 2007-04-18 | 2008-10-23 | Moore Margaret D | Single chain fc, methods of making and methods of treatment |
| WO2008131575A2 (en) | 2007-04-27 | 2008-11-06 | Esbatech Ag | Anti-alk antibodies suitable for treating metastatic cancers or tumors |
| BRPI0811857A2 (pt) | 2007-05-14 | 2014-10-21 | Biogen Idec Inc | Regiões fc (scfc) de cadeia simples, polipeptídeos de aglutinação que as compreendem e métodos relacionados. |
| EP2014681A1 (en) | 2007-07-12 | 2009-01-14 | Pierre Fabre Medicament | Novel antibodies inhibiting c-met dimerization, and uses thereof |
| CA2700815A1 (en) | 2007-09-27 | 2009-04-02 | Viventia Biotech Inc. | Optimized nucleic acid sequences for the expression of vb4-845 |
| EP2220121B1 (en) | 2007-11-12 | 2015-08-19 | U3 Pharma GmbH | Axl antibodies |
| CL2008003449A1 (es) | 2007-11-21 | 2010-02-19 | Imclone Llc | Anticuerpo o fragmentos del mismo contra el receptor de proteína estimulante de macrófagos/ron; composición farmacéutica que lo comprende; uso para inhibir angiogénesis, crecimiento tumoral, proliferación, migración e invasión de células tumorales, activación de ron o fosforilación de mapk y/o akt; y uso para tratar cáncer. |
| PT2235064E (pt) | 2008-01-07 | 2016-03-01 | Amgen Inc | Método de preparação de moléculas heterodiméricas de fc de anticorpos utilizando efeitos de indução eletrostática |
| BRPI0906498A2 (pt) | 2008-01-22 | 2015-07-14 | Biogen Idec Inc | Anticorpo ron e seus usos |
| MX2010011145A (es) * | 2008-04-11 | 2011-04-11 | Merrimack Pharmaceuticals Inc | Enlazadores de la albumina de suero humana y conjugados de la misma. |
| US20100009390A1 (en) | 2008-05-09 | 2010-01-14 | The Regents Of The University Of California | Mutant antibodies with high affinity for egfr |
| WO2010002862A2 (en) | 2008-07-01 | 2010-01-07 | Aveo Pharmaceuticals, Inc. | Fibroblast growth factor receptor 3 (fgfr3) binding proteins |
| WO2010064090A1 (en) | 2008-12-02 | 2010-06-10 | Pierre Fabre Medicament | Process for the modulation of the antagonistic activity of a monoclonal antibody |
| MX2011010158A (es) | 2009-04-07 | 2011-10-17 | Roche Glycart Ag | Anticuerpos biespecificos anti-erbb-2/anti-c-met. |
| MX2011012136A (es) | 2009-05-15 | 2012-04-10 | Chugai Pharmaceutical Co Ltd | Anticuerpo anti-axl. |
| GB0909904D0 (en) * | 2009-06-09 | 2009-07-22 | Affitech As | Product |
| US9493578B2 (en) * | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| TWI600760B (zh) | 2009-11-05 | 2017-10-01 | 建南德克公司 | 分泌異源多肽之方法及組合物 |
| RS66008B1 (sr) | 2010-03-10 | 2024-10-31 | Genmab As | Monoklonska antitela protiv c-met |
| WO2011136911A2 (en) | 2010-04-09 | 2011-11-03 | Aveo Pharmaceuticals, Inc. | Anti-erbb3 antibodies |
| SG185487A1 (en) | 2010-05-11 | 2012-12-28 | Aveo Pharmaceuticals Inc | Anti-fgfr2 antibodies |
| WO2011159980A1 (en) | 2010-06-18 | 2011-12-22 | Genentech, Inc. | Anti-axl antibodies and methods of use |
| CA2804399A1 (en) | 2010-07-06 | 2012-01-12 | Aveo Pharmaceuticals, Inc. | Anti-ron antibodies |
| WO2012006635A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Processable single chain molecules and polypeptides made using same |
| WO2013033008A2 (en) | 2011-08-26 | 2013-03-07 | Merrimack Pharmaceuticals, Inc. | Tandem fc bispecific antibodies |
| MX2015011712A (es) * | 2013-03-06 | 2016-04-04 | Merrimack Pharmaceuticals Inc | Anticerpos biespecificos fc en fila anti-c-met. |
-
2014
- 2014-03-06 MX MX2015011712A patent/MX2015011712A/es unknown
- 2014-03-06 AU AU2014225661A patent/AU2014225661A1/en not_active Abandoned
- 2014-03-06 CA CA2902505A patent/CA2902505A1/en not_active Abandoned
- 2014-03-06 CN CN201480025963.5A patent/CN105705519A/zh active Pending
- 2014-03-06 TW TW103107787A patent/TW201444872A/zh unknown
- 2014-03-06 US US14/199,760 patent/US9458245B2/en not_active Expired - Fee Related
- 2014-03-06 SG SG11201506451UA patent/SG11201506451UA/en unknown
- 2014-03-06 EA EA201591652A patent/EA201591652A1/ru unknown
- 2014-03-06 BR BR112015021462A patent/BR112015021462A2/pt not_active IP Right Cessation
- 2014-03-06 HK HK16108077.1A patent/HK1220465A1/zh unknown
- 2014-03-06 WO PCT/US2014/021341 patent/WO2014138449A1/en not_active Ceased
- 2014-03-06 JP JP2015561668A patent/JP2016510755A/ja active Pending
- 2014-03-06 KR KR1020157026790A patent/KR20150143458A/ko not_active Withdrawn
- 2014-03-06 EP EP14717252.2A patent/EP2964676A1/en not_active Withdrawn
-
2015
- 2015-08-16 IL IL240594A patent/IL240594A0/en unknown
-
2016
- 2016-09-30 US US15/282,421 patent/US20170081421A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180101623A (ko) * | 2016-02-03 | 2018-09-12 | 암젠 리서치 (뮌헨) 게엠베하 | Psma 및 cd3 이중특이성 t 세포 맞물림 항체 작제물 |
| KR20180103084A (ko) * | 2016-02-03 | 2018-09-18 | 암젠 리서치 (뮌헨) 게엠베하 | Bcma 및 cd3 이중특이성 t 세포 맞물림 항체 작제물 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105705519A (zh) | 2016-06-22 |
| BR112015021462A2 (pt) | 2017-10-10 |
| SG11201506451UA (en) | 2015-09-29 |
| AU2014225661A1 (en) | 2015-09-10 |
| US20170081421A1 (en) | 2017-03-23 |
| WO2014138449A1 (en) | 2014-09-12 |
| US9458245B2 (en) | 2016-10-04 |
| MX2015011712A (es) | 2016-04-04 |
| CA2902505A1 (en) | 2014-09-12 |
| TW201444872A (zh) | 2014-12-01 |
| EA201591652A1 (ru) | 2016-02-29 |
| JP2016510755A (ja) | 2016-04-11 |
| IL240594A0 (en) | 2015-09-24 |
| US20140302035A1 (en) | 2014-10-09 |
| HK1220465A1 (zh) | 2017-05-05 |
| EP2964676A1 (en) | 2016-01-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9458245B2 (en) | ANTI-C-MET tandem Fc bispecific antibodies | |
| US20170218028A1 (en) | Tandem fc bispecific antibodies | |
| US11377477B2 (en) | PD-1 targeted IL-15/IL-15RALPHA fc fusion proteins and uses in combination therapies thereof | |
| KR101517320B1 (ko) | 단일특이적 및 이중특이적 항-igf-1r 및 항 erbb3 항체 | |
| JP2016510755A5 (enExample) | ||
| US20240010748A1 (en) | Bispecific antibody for claudin 18a2 and cd3 and application of bispecific antibody | |
| CA3201518A1 (en) | Bi-functional molecules | |
| WO2022242679A1 (en) | Anti-cd137 antibodies and methods of use | |
| US12473367B2 (en) | Bispecific agonistic antibodies to activin a receptor like type 1 (ALK1) | |
| US20240383990A1 (en) | Hinge-modified bispecific antibodies | |
| US20240209113A1 (en) | Anti-gpc3 and anti-cd137 multispecific antibodies and methods of use | |
| WO2024243048A1 (en) | Bispecific agonistic antibodies to il12 receptor | |
| KR20250168499A (ko) | 액티빈 a 수용체 유사 유형 1(alk1)에 대한 이중 특이적 효현성 항체 | |
| HK40014565A (en) | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20150925 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20151203 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |