EA015580B1 - Моноклональное анти-мет антитело, его фрагменты и векторы для лечения опухолей и соответствующие продукты - Google Patents
Моноклональное анти-мет антитело, его фрагменты и векторы для лечения опухолей и соответствующие продукты Download PDFInfo
- Publication number
- EA015580B1 EA015580B1 EA200870234A EA200870234A EA015580B1 EA 015580 B1 EA015580 B1 EA 015580B1 EA 200870234 A EA200870234 A EA 200870234A EA 200870234 A EA200870234 A EA 200870234A EA 015580 B1 EA015580 B1 EA 015580B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- met
- antibody
- sec
- cells
- spk
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 91
- 239000013598 vector Substances 0.000 title claims abstract description 55
- 238000011282 treatment Methods 0.000 title claims abstract description 40
- 239000012634 fragment Substances 0.000 title claims abstract description 29
- 206010027476 Metastases Diseases 0.000 claims abstract description 27
- 239000002773 nucleotide Substances 0.000 claims abstract description 18
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 11
- 229940043355 kinase inhibitor Drugs 0.000 claims abstract description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 27
- 108090000623 proteins and genes Proteins 0.000 claims description 19
- -1 2,6-dichlorobenzyl Chemical group 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 13
- 210000004408 hybridoma Anatomy 0.000 claims description 12
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 230000009401 metastasis Effects 0.000 claims description 7
- 230000006337 proteolytic cleavage Effects 0.000 claims description 6
- 238000005516 engineering process Methods 0.000 claims description 5
- 239000007791 liquid phase Substances 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 2
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical class C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 108020004511 Recombinant DNA Proteins 0.000 claims 4
- 238000010532 solid phase synthesis reaction Methods 0.000 claims 4
- 238000001802 infusion Methods 0.000 claims 2
- 229940124530 sulfonamide Drugs 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 210000005170 neoplastic cell Anatomy 0.000 abstract description 9
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 abstract description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 175
- 102000005962 receptors Human genes 0.000 description 43
- 108020003175 receptors Proteins 0.000 description 43
- 101150053038 NORK gene Proteins 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 34
- 230000001629 suppression Effects 0.000 description 31
- 230000004913 activation Effects 0.000 description 25
- 150000001413 amino acids Chemical group 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 24
- 238000012360 testing method Methods 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 20
- 239000013592 cell lysate Substances 0.000 description 19
- 238000001262 western blot Methods 0.000 description 19
- 230000000694 effects Effects 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 230000012010 growth Effects 0.000 description 15
- 238000004873 anchoring Methods 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 239000003636 conditioned culture medium Substances 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 230000004614 tumor growth Effects 0.000 description 12
- 108091007163 high choriolytic enzyme Proteins 0.000 description 11
- 230000006907 apoptotic process Effects 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 230000001419 dependent effect Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 9
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 9
- 238000001114 immunoprecipitation Methods 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- 230000003211 malignant effect Effects 0.000 description 8
- 229920001817 Agar Polymers 0.000 description 7
- 102000035195 Peptidases Human genes 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 230000037361 pathway Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 230000009545 invasion Effects 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- UPZUHYMBTUUPML-XGUBFFRZSA-N (1S,2S,3R,6S)-4-(hydroxymethyl)-6-(octylamino)cyclohex-4-ene-1,2,3-triol Chemical compound CCCCCCCCN[C@H]1C=C(CO)[C@@H](O)[C@H](O)[C@H]1O UPZUHYMBTUUPML-XGUBFFRZSA-N 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 5
- 241000782624 Zema Species 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000012228 culture supernatant Substances 0.000 description 5
- 238000011532 immunohistochemical staining Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 241000283707 Capra Species 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 4
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 4
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 4
- 230000001270 agonistic effect Effects 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- 239000012133 immunoprecipitate Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 235000002374 tyrosine Nutrition 0.000 description 4
- YNZXLMPHTZVKJN-VBKCWIKWSA-N (3z,5e,7r,8r,9s,10s,11r,13e,15e,17s,18r)-18-[(2s,3r,4s)-4-[(2r,4r,5s,6r)-2,4-dihydroxy-5-methyl-6-[(e)-prop-1-enyl]oxan-2-yl]-3-hydroxypentan-2-yl]-9-ethyl-8,10-dihydroxy-3,17-dimethoxy-5,7,11,13-tetramethyl-1-oxacyclooctadeca-3,5,13,15-tetraen-2-one Chemical compound O1C(=O)\C(OC)=C\C(\C)=C\[C@@H](C)[C@@H](O)[C@@H](CC)[C@@H](O)[C@H](C)C\C(C)=C\C=C\[C@H](OC)[C@H]1[C@@H](C)[C@@H](O)[C@H](C)[C@]1(O)O[C@H](\C=C\C)[C@@H](C)[C@H](O)C1 YNZXLMPHTZVKJN-VBKCWIKWSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 description 3
- 102000043136 MAP kinase family Human genes 0.000 description 3
- 108091054455 MAP kinase family Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 108090000848 Ubiquitin Proteins 0.000 description 3
- 102000044159 Ubiquitin Human genes 0.000 description 3
- 239000002870 angiogenesis inducing agent Substances 0.000 description 3
- 230000000711 cancerogenic effect Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 229930184793 concanamycin Natural products 0.000 description 3
- 230000006552 constitutive activation Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 230000012202 endocytosis Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000029578 entry into host Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- NHZLNPMOSADWGC-UHFFFAOYSA-N 4-amino-N-(2-quinoxalinyl)benzenesulfonamide Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CN=C(C=CC=C2)C2=N1 NHZLNPMOSADWGC-UHFFFAOYSA-N 0.000 description 2
- 108091005508 Acid proteases Proteins 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- 102000043859 Dynamin Human genes 0.000 description 2
- 108700021058 Dynamin Proteins 0.000 description 2
- 102220550861 Dynamin-3_K44A_mutation Human genes 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
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
- 101150105382 MET gene Proteins 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 101100450271 Oryzias latipes hceb gene Proteins 0.000 description 2
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 2
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100025292 Stress-induced-phosphoprotein 1 Human genes 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 2
- 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 2
- 229960002576 amiloride Drugs 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000002457 bidirectional effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000004709 cell invasion Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000006395 clathrin-mediated endocytosis Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 208000010749 gastric carcinoma Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
- 108010052968 leupeptin Proteins 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 108010091212 pepstatin Proteins 0.000 description 2
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- 229920002704 polyhistidine Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 201000000498 stomach carcinoma Diseases 0.000 description 2
- 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 2
- 239000000758 substrate Substances 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 150000003668 tyrosines Chemical class 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101150116779 CD82 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 108010049207 Death Domain Receptors Proteins 0.000 description 1
- 102000009058 Death Domain Receptors Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 101150020891 PRKCA gene Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 102400000827 Saposin-D Human genes 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 241000613085 Ulesta Species 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 102000038380 alpha-secretases Human genes 0.000 description 1
- 108091007736 alpha-secretases Proteins 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000025164 anoikis Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000006368 anti-apoptosis response Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000015916 branching morphogenesis of a tube Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000013210 hematogenous Diseases 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000001466 metabolic labeling Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000034918 positive regulation of cell growth Effects 0.000 description 1
- 230000016833 positive regulation of signal transduction Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 239000003805 procoagulant Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000026938 proteasomal ubiquitin-dependent protein catabolic process Effects 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011158 quantitative evaluation Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000002226 simultaneous effect Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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
- C07K16/2863—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
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/867—Retroviral vectors
-
- 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
- C07K2317/70—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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/027—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a retrovirus
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06101345 | 2006-02-06 | ||
| PCT/EP2007/051066 WO2007090807A1 (en) | 2006-02-06 | 2007-02-05 | Anti-met monoclonal antibody, fragments and vectors thereof, for the treatment of tumors and corresponding products |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200870234A1 EA200870234A1 (ru) | 2009-02-27 |
| EA015580B1 true EA015580B1 (ru) | 2011-10-31 |
Family
ID=36616994
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200870234A EA015580B1 (ru) | 2006-02-06 | 2007-02-05 | Моноклональное анти-мет антитело, его фрагменты и векторы для лечения опухолей и соответствующие продукты |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US8388958B2 (OSRAM) |
| EP (2) | EP2192188A1 (OSRAM) |
| JP (1) | JP5306828B2 (OSRAM) |
| KR (1) | KR101429297B1 (OSRAM) |
| CN (1) | CN101379192B (OSRAM) |
| AT (1) | ATE514715T1 (OSRAM) |
| AU (1) | AU2007213804B2 (OSRAM) |
| BR (1) | BRPI0707480A8 (OSRAM) |
| CA (1) | CA2638889C (OSRAM) |
| CY (1) | CY1111884T1 (OSRAM) |
| DK (1) | DK1981981T3 (OSRAM) |
| EA (1) | EA015580B1 (OSRAM) |
| ES (1) | ES2368864T3 (OSRAM) |
| IL (1) | IL192879A (OSRAM) |
| MX (1) | MX2008009833A (OSRAM) |
| PL (1) | PL1981981T3 (OSRAM) |
| PT (1) | PT1981981E (OSRAM) |
| SG (2) | SG169382A1 (OSRAM) |
| SI (1) | SI1981981T1 (OSRAM) |
| WO (1) | WO2007090807A1 (OSRAM) |
| ZA (1) | ZA200806559B (OSRAM) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2014681A1 (en) | 2007-07-12 | 2009-01-14 | Pierre Fabre Medicament | Novel antibodies inhibiting c-met dimerization, and uses thereof |
| IL198545A0 (en) | 2008-05-14 | 2011-07-31 | Metheresis Translational Res Sa | High affinity binding site of hgfr and methods for identification of antagonists thereof |
| EP2127683A1 (en) * | 2008-05-29 | 2009-12-02 | Metheresis Translational Research SA | Anti-Met monoclonal antibody, fragments and derivatives thereof for use in tumor imaging, corresponding compositions and kits |
| PA8849001A1 (es) | 2008-11-21 | 2010-06-28 | Lilly Co Eli | Anticuerpos de c-met |
| EP2287197A1 (en) * | 2009-08-21 | 2011-02-23 | Pierre Fabre Medicament | Anti-cMET antibody and its use for the detection and the diagnosis of cancer |
| KR101671378B1 (ko) | 2009-10-30 | 2016-11-01 | 삼성전자 주식회사 | ｃ-Ｍｅｔ에 특이적으로 결합하는 항체 및 그의 용도 |
| KR101748707B1 (ko) * | 2009-11-27 | 2017-06-20 | 삼성전자주식회사 | ｃ-Ｍｅｔ에 특이적으로 결합하는 항체 및 그를 이용한 암 진단용 키트 |
| EP3511342B1 (en) | 2010-03-10 | 2024-01-17 | Genmab A/S | Monoclonal antibodies against c-met |
| WO2011125458A1 (ja) | 2010-04-02 | 2011-10-13 | 富士レビオ株式会社 | 抗癌剤の効果の診断用マーカー |
| EP2808344A1 (en) * | 2010-06-01 | 2014-12-03 | Monash University | Antibodies directed to the receptor tyrosine kinase c-Met |
| RU2013114783A (ru) * | 2010-09-03 | 2014-10-10 | Академиа Синика | Anti-с-мет антитела и способы их применения |
| BR122014027420A2 (pt) | 2010-11-03 | 2019-08-20 | Argenx Bvba | Anticorpos anti c-met |
| ES2489475T3 (es) * | 2011-03-18 | 2014-09-02 | Metheresis Translational Research Sa | Inhibidores MET para potenciar la eficacia de la radioterapia |
| WO2013043452A1 (en) | 2011-09-20 | 2013-03-28 | Eli Lilly And Company | Anti-c-met antibodies |
| EP2773660A2 (en) | 2011-11-03 | 2014-09-10 | Argen-X B.V. | Chimeric human-camel antigens and their use |
| BR112014012005A2 (pt) | 2011-11-21 | 2017-12-19 | Genentech Inc | composições, métodos, formulação farmacêutica e artigo |
| WO2013079973A1 (en) | 2011-12-02 | 2013-06-06 | Di Cara Danielle Marie | Antibodies against hgf - receptor and uses |
| US8900582B2 (en) | 2011-12-22 | 2014-12-02 | Samsung Electronics Co., Ltd. | Deimmunized anti c-Met humanized antibodies and uses thereof |
| CN103382223B (zh) * | 2012-04-01 | 2015-06-10 | 上海益杰生物技术有限公司 | 针对表皮生长因子受体隐蔽表位和t细胞抗原的多功能抗体多肽 |
| EP2863946A4 (en) * | 2012-06-21 | 2016-04-13 | Sorrento Therapeutics Inc | ANTIGEN-BINDING PROTEINS THAT BIND TO C-MET |
| ITTO20130012A1 (it) | 2013-01-09 | 2014-07-10 | Metheresis Translational Res S A | Nuovi frammenti anticorpali, relative composizioni ed usi |
| KR102200274B1 (ko) | 2014-09-16 | 2021-01-08 | 심포젠 에이/에스 | 항-ｍｅｔ 항체 및 조성물 |
| WO2016149116A1 (en) * | 2015-03-13 | 2016-09-22 | University Of Maryland, Baltimore | Antibodies targeting s100b and methods of use |
| US20180057595A1 (en) | 2015-03-16 | 2018-03-01 | Celldex Therapeutics, Inc. | Anti-MET Antibodies and Methods of Use Thereof |
| IT201800000534A1 (it) * | 2018-01-03 | 2019-07-03 | Procedimenti per la promozione della crescita cellulare degli isolotti pancreatici. | |
| GB201611123D0 (en) | 2016-06-27 | 2016-08-10 | Euremab Srl | Anti met antibodiesand uses thereof |
| JP6942179B2 (ja) * | 2016-09-29 | 2021-09-29 | 田辺三菱製薬株式会社 | ｃＭＥＴモノクローナル結合剤、その薬物複合体およびその使用 |
| 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 |
| CN106872695B (zh) * | 2017-01-20 | 2019-06-11 | 中山大学 | 一种h7亚型禽流感病毒血凝素抗体间接elisa检测试剂盒 |
| IT201800000535A1 (it) | 2018-01-03 | 2019-07-03 | Procedimenti per la cura del cancro. | |
| IT201800003875A1 (it) * | 2018-03-22 | 2019-09-22 | Metis Prec Medicine Sb S R L | Nuova combinazione di agenti terapeutici per il trattamento di un tumore e/o metastasi |
| WO2019189453A1 (en) | 2018-03-28 | 2019-10-03 | Mitsubishi Tanabe Pharma Corporation | DRUG CONJUGATES OF cMET MONOCLONAL BINDING AGENTS, AND USES THEREOF |
| IT201800009282A1 (it) | 2018-10-09 | 2020-04-09 | Metis Prec Medicine Sb Srl | Nuovo agente terapeutico per il trattamento di un tumore e/o metastasi |
| CN114340684B (zh) | 2019-09-16 | 2025-09-12 | 瑞泽恩制药公司 | 用于免疫pet成像的放射性标记的met结合蛋白 |
| WO2024246356A1 (en) | 2023-06-01 | 2024-12-05 | Pierre Fabre Medicament | Silenced antibody-based anti-met constructs for the treatment of tumors and metastasis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6214344B1 (en) * | 1995-06-02 | 2001-04-10 | Genetech, Inc. | Hepatocyte growth factor receptor antagonists and uses thereof |
| WO2005016382A1 (en) * | 2003-08-04 | 2005-02-24 | Pfizer Products Inc. | Antibodies to c-met |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CU22545A1 (es) * | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
| US6814962B1 (en) | 1994-06-02 | 2004-11-09 | Aventis Pharma S.A. | Recombinant viruses and their use for treatment of atherosclerosis and other forms of coronary artery disease and method, reagent, and kit for evaluating susceptibility to same |
-
2007
- 2007-02-05 US US12/223,623 patent/US8388958B2/en active Active
- 2007-02-05 EP EP10151809A patent/EP2192188A1/en not_active Withdrawn
- 2007-02-05 CN CN2007800047097A patent/CN101379192B/zh active Active
- 2007-02-05 MX MX2008009833A patent/MX2008009833A/es active IP Right Grant
- 2007-02-05 ES ES07704350T patent/ES2368864T3/es active Active
- 2007-02-05 BR BRPI0707480A patent/BRPI0707480A8/pt not_active Application Discontinuation
- 2007-02-05 EA EA200870234A patent/EA015580B1/ru not_active IP Right Cessation
- 2007-02-05 SG SG201100805-9A patent/SG169382A1/en unknown
- 2007-02-05 WO PCT/EP2007/051066 patent/WO2007090807A1/en not_active Ceased
- 2007-02-05 SI SI200730720T patent/SI1981981T1/sl unknown
- 2007-02-05 KR KR1020087016543A patent/KR101429297B1/ko active Active
- 2007-02-05 PT PT07704350T patent/PT1981981E/pt unknown
- 2007-02-05 CA CA2638889A patent/CA2638889C/en active Active
- 2007-02-05 SG SG201100806-7A patent/SG169383A1/en unknown
- 2007-02-05 EP EP07704350A patent/EP1981981B1/en active Active
- 2007-02-05 DK DK07704350.3T patent/DK1981981T3/da active
- 2007-02-05 PL PL07704350T patent/PL1981981T3/pl unknown
- 2007-02-05 AT AT07704350T patent/ATE514715T1/de active
- 2007-02-05 JP JP2008553739A patent/JP5306828B2/ja active Active
- 2007-02-05 AU AU2007213804A patent/AU2007213804B2/en active Active
-
2008
- 2008-07-17 IL IL192879A patent/IL192879A/en active IP Right Grant
- 2008-07-28 ZA ZA2008/06559A patent/ZA200806559B/en unknown
-
2011
- 2011-09-26 CY CY20111100926T patent/CY1111884T1/el unknown
- 2011-11-04 US US13/373,101 patent/US8729043B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6214344B1 (en) * | 1995-06-02 | 2001-04-10 | Genetech, Inc. | Hepatocyte growth factor receptor antagonists and uses thereof |
| WO2005016382A1 (en) * | 2003-08-04 | 2005-02-24 | Pfizer Products Inc. | Antibodies to c-met |
Non-Patent Citations (10)
| Title |
|---|
| AMENDOLA MARIO ET AL.: "Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters" NATURE BIOTECHNOLOGY, vol. 23, no. 1, January 2005 (2005-01), pages 108-116, XP002389318 ISSN: 1087-0156 pages 108-110 * |
| BALYASNIKOVA IRINA V. ET AL.: "Epitope-specific antibody-induced cleavage of angiotensin-converting enzyme from the cell surface" BIOCHEMICAL JOURNAL, vol. 362, no. 3, 15 March 2002 (2002-03-15), pages 585-595, XP002389317 ISSN: 0264-6021 the whole document * |
| BARDELLI ET AL.: "Agonist Met antibodies define the signalling threshold required for a full mitogenic and invasive program of Kaposi's Sarcoma cells" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ACADEMIC PRESS INC. ORLANDO, FL, US, vol. 334, no. 4, 9 September 2005 (2005-09-09), pages 1172-1179, XP005001511 ISSN: 0006-291X figure 2 * |
| CORTESINA G. ET AL.: "Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases." INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER 20 MAY 2000, vol. 89, no. 3, 20 May 2000 (2000-05-20), pages 286-292, XP002430067 ISSN: 0020-7136 page 286 - page 288 figure 2 * |
| GALVANI ARTURO P. ET AL.: "Suramin modulates cellular levels of hepatocyte growth factor receptor by inducing shedding of a soluble form" BIOCHEMICAL PHARMACOLOGY, vol. 50, no. 7, 1995, pages 959-966, XP002389315 ISSN: 0006-2952 figure 1 * |
| HAY RICK V. ET AL.: "Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek)." CLINICAL CANCER RESEARCH : AN OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH 1 OST 2005, vol. 11, no. 19 Pt 2, 1 October 2005 (2005-10-01), pages 7064s-7069s, XP002430068 ISSN: 1078-0432 figures 1-4 * |
| MICHIELI PAOLO ET AL.: "Targeting the tumor and its microenvironment by a dual-function decoy Met receptor" CANCER CELL, vol. 6, no. 1, July 2004 (2004-07), pages 61-73, XP002389313 ISSN: 1535-6108 cited in the application the whole document * |
| PETRELLI A. ET AL.: "Ab-induced ectodomain shedding mediates hepatocytes growth factor receptor down-regulation and hampers biological activity" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 28 MAR 2006 UNITED STATES, vol. 103, no. 13, 28 March 2006 (2006-03-28), pages 5090-5095, XP002389316 ISSN: 0027-8424 page 5095, column 1, lines 12-14 * |
| PRAT M. ET AL.: "AGONISTIC MONOCLONAL ANTIBODIES AGAINST THE MET RECEPTOR DISSECT THE BIOLOGICAL RESPONSES TO HGF" JOURNAL OF CELL SCIENCE, CAMBRIDGE UNIVERSITY PRESS, LONDON, GB, vol. 111, no. PART 2, 1998, pages 237-247, XP000943567 ISSN: 0021-9533 cited in the application page 243 - page 244 pages 240-244 figure 8 * |
| WAJIH NADEEM ET AL.: "Vascular origin of a soluble truncated form of the hepatocyte growth factor receptor (c-met)" CIRCULATION RESEARCH, vol. 90, no. 1, 11 January 2002 (2002-01-11), pages 46-52, XP002389314 ISSN: 0009-7330 figures 4,6 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA015580B1 (ru) | Моноклональное анти-мет антитело, его фрагменты и векторы для лечения опухолей и соответствующие продукты | |
| Valencia et al. | Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces cell survival, homing, and colonization in lung cancer bone metastasis | |
| Leone et al. | Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm3-transfected melanoma cells | |
| JP5572718B2 (ja) | 乳癌を処置するための方法 | |
| Yang et al. | Semaphorin 4D promotes skeletal metastasis in breast cancer | |
| US6767541B2 (en) | HER-2/neu overexpression abrogates growth inhibitory pathways | |
| JP2005530687A (ja) | Ｆｇｆｒアゴニスト | |
| US20100111964A1 (en) | Pleiotrophin growth factor receptor for the treatment of proliferative, vascular and neurological disorders | |
| JP6871866B2 (ja) | 抗ｒｈｏ ｇｔｐａｓｅコンホーメーションシングルドメイン抗体及びその使用 | |
| US20090123462A1 (en) | Fgfr agonists | |
| US20060234271A1 (en) | Methods for the diagnosis and treatment of metastatic prostate tumors | |
| US20080020461A1 (en) | Kinesin-like proteins and methods of use | |
| US20210379147A1 (en) | Method and system for treating cancer utilizing tinagl1 | |
| US9383364B2 (en) | Predictive marker of DNMT1 inhibitor therapeutic efficacy and methods of using the marker | |
| KR100877824B1 (ko) | Ｅ2ｅｐｆ ｕｃｐ-ｖｈｌ 상호작용 및 그 용도 | |
| Jakowlew | Transforming growth factor-β in lung cancer, carcinogenesis, and metastasis | |
| KR20190040585A (ko) | Human Stm1 (hStm1) 유전자의 발현 또는 hSTM1 단백질의 활성을 억제하는 물질을 포함하는, 위암의 예방 또는 치료용 약학적 조성물 | |
| Ha | Distinct ShcA Signaling Complexes Influence Breast Tumor Growth and Resistance to Tyrosine Kinase Inhibitors | |
| Eccles | Models for evaluation of targeted therapies of invasive and metastatic disease | |
| McCarthy | A role for TRPV6 ion channels in prostate cancer bone metastases | |
| KR20080071950A (ko) | Ｐｕｍａ의 암 침윤 또는 전이 표적으로서의 용도 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM |