EA021584B1 - Ингибитор рецептора фактора роста фибробластов-3 (fgfr-3) и его применение - Google Patents
Ингибитор рецептора фактора роста фибробластов-3 (fgfr-3) и его применение Download PDFInfo
- Publication number
- EA021584B1 EA021584B1 EA201170590A EA201170590A EA021584B1 EA 021584 B1 EA021584 B1 EA 021584B1 EA 201170590 A EA201170590 A EA 201170590A EA 201170590 A EA201170590 A EA 201170590A EA 021584 B1 EA021584 B1 EA 021584B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- antibody
- popk
- zeg
- cells
- rgo
- Prior art date
Links
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 title abstract 2
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 title abstract 2
- 239000003112 inhibitor Substances 0.000 title 1
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 49
- 239000012634 fragment Substances 0.000 claims abstract description 36
- 201000011510 cancer Diseases 0.000 claims abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 241000282414 Homo sapiens Species 0.000 claims description 50
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 16
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 101000709250 Homo sapiens Serine/threonine-protein kinase SIK2 Proteins 0.000 claims 1
- 102100034377 Serine/threonine-protein kinase SIK2 Human genes 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 32
- 101000917148 Homo sapiens Fibroblast growth factor receptor 3 Proteins 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 115
- 230000027455 binding Effects 0.000 description 83
- 239000000523 sample Substances 0.000 description 51
- 102000005962 receptors Human genes 0.000 description 50
- 108020003175 receptors Proteins 0.000 description 50
- 238000011282 treatment Methods 0.000 description 32
- 108090000623 proteins and genes Proteins 0.000 description 31
- 102000004169 proteins and genes Human genes 0.000 description 28
- 235000018102 proteins Nutrition 0.000 description 26
- 229960004316 cisplatin Drugs 0.000 description 23
- 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 22
- 239000003446 ligand Substances 0.000 description 22
- 239000002953 phosphate buffered saline Substances 0.000 description 22
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- 239000000427 antigen Substances 0.000 description 20
- 230000004913 activation Effects 0.000 description 19
- 102000036639 antigens Human genes 0.000 description 19
- 108091007433 antigens Proteins 0.000 description 19
- 210000004881 tumor cell Anatomy 0.000 description 19
- 239000013598 vector Substances 0.000 description 19
- 230000035772 mutation Effects 0.000 description 17
- 102000043136 MAP kinase family Human genes 0.000 description 15
- 108091054455 MAP kinase family Proteins 0.000 description 15
- 101150025129 POP1 gene Proteins 0.000 description 15
- 238000001262 western blot Methods 0.000 description 15
- 230000000903 blocking effect Effects 0.000 description 13
- 239000001963 growth medium Substances 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 239000002957 persistent organic pollutant Substances 0.000 description 11
- 230000008054 signal transmission Effects 0.000 description 11
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 230000019491 signal transduction Effects 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 206010035226 Plasma cell myeloma Diseases 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 102220469221 S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1B_E18A_mutation Human genes 0.000 description 8
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000006166 lysate Substances 0.000 description 8
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 8
- 101100000208 Mus musculus Orm2 gene Proteins 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 229940127089 cytotoxic agent Drugs 0.000 description 7
- 239000012636 effector Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 208000034578 Multiple myelomas Diseases 0.000 description 6
- 235000004279 alanine Nutrition 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000001962 electrophoresis Methods 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 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 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 206010005003 Bladder cancer Diseases 0.000 description 5
- 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 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000002254 cytotoxic agent Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 210000004602 germ cell Anatomy 0.000 description 5
- 229960002897 heparin Drugs 0.000 description 5
- 229920000669 heparin Polymers 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 229910052707 ruthenium Inorganic materials 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 102220624923 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1_E8A_mutation Human genes 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 231100000599 cytotoxic agent Toxicity 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 201000005112 urinary bladder cancer Diseases 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 230000001270 agonistic effect Effects 0.000 description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000012148 binding buffer Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000006552 constitutive activation Effects 0.000 description 3
- 239000013068 control sample Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 230000012202 endocytosis Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 108010082117 matrigel Proteins 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229950010131 puromycin Drugs 0.000 description 3
- 238000004445 quantitative analysis Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 101100148273 Chlorobaculum tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS) rub3 gene Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 101100460719 Mus musculus Noto gene Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- -1 actinomycin-Ό Chemical compound 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 238000004091 panning Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 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 2
- 230000008569 process Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000010186 staining Methods 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
- 239000003826 tablet Substances 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000003313 weakening effect Effects 0.000 description 2
- IPDRTIBDOPMMIQ-VAOFZXAKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)-2-methyloxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@]1(C)O[C@H](CO)[C@@H](O)C1 IPDRTIBDOPMMIQ-VAOFZXAKSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- BZSVVCFHMVMYCR-UHFFFAOYSA-N 2-pyridin-2-ylpyridine;ruthenium Chemical compound [Ru].N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1 BZSVVCFHMVMYCR-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 101000689231 Aeromonas salmonicida S-layer protein Proteins 0.000 description 1
- 108010037870 Anthranilate Synthase Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102100035833 Histo-blood group ABO system transferase Human genes 0.000 description 1
- 101710142776 Histo-blood group ABO system transferase Proteins 0.000 description 1
- 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100172512 Mus musculus Epha2 gene Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010070308 Refractory cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241001424341 Tara spinosa Species 0.000 description 1
- 101000748795 Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) Cytochrome c oxidase polypeptide I+III Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 101100187345 Xenopus laevis noto gene Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 229950008560 almecillin Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 206010005084 bladder transitional cell carcinoma Diseases 0.000 description 1
- 201000001528 bladder urothelial carcinoma Diseases 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000057230 human FGF3 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000003331 infrared imaging Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- QULKGELYPOJSLP-WCABBAIRSA-N penicillin O Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2[C@H](NC(=O)CSCC=C)C(=O)N21 QULKGELYPOJSLP-WCABBAIRSA-N 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 230000016833 positive regulation of signal transduction Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 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
-
- 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
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
- C07K16/46—Hybrid immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
- C07K2317/70—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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19685508P | 2008-10-20 | 2008-10-20 | |
| PCT/US2009/060840 WO2010048026A2 (en) | 2008-10-20 | 2009-10-15 | Fibroblast growth factor receptor-3 (fgfr-3) inhibitors and methods of treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201170590A1 EA201170590A1 (ru) | 2011-10-31 |
| EA021584B1 true EA021584B1 (ru) | 2015-07-30 |
Family
ID=42062445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201170590A EA021584B1 (ru) | 2008-10-20 | 2009-10-15 | Ингибитор рецептора фактора роста фибробластов-3 (fgfr-3) и его применение |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US8043618B2 (enExample) |
| EP (1) | EP2342232A2 (enExample) |
| JP (1) | JP5577345B2 (enExample) |
| KR (1) | KR101370798B1 (enExample) |
| CN (2) | CN103524620A (enExample) |
| AR (1) | AR073770A1 (enExample) |
| AU (1) | AU2009307841B2 (enExample) |
| BR (1) | BRPI0919832A8 (enExample) |
| CA (1) | CA2741127C (enExample) |
| EA (1) | EA021584B1 (enExample) |
| IL (1) | IL211807A0 (enExample) |
| MX (1) | MX2011004317A (enExample) |
| NZ (1) | NZ592369A (enExample) |
| TW (1) | TWI381848B (enExample) |
| UA (1) | UA101681C2 (enExample) |
| WO (1) | WO2010048026A2 (enExample) |
| ZA (1) | ZA201101938B (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI381848B (zh) * | 2008-10-20 | 2013-01-11 | Imclone Llc | 抗纖維母細胞生長因子受體-3 (fgfr-3) 抗體及包含其之醫藥組合物 |
| HUE061117T2 (hu) | 2009-03-25 | 2023-05-28 | Genentech Inc | Anti-FGFR3 antitestek és eljárások alkalmazásukra |
| WO2013088191A1 (en) | 2011-12-12 | 2013-06-20 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Antagonist of the fibroblast growth factor receptor 3 (fgfr3) for use in the treatment or the prevention of skeletal disorders linked with abnormal activation of fgfr3 |
| WO2014111744A1 (en) | 2013-01-16 | 2014-07-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A soluble fibroblast growth factor receptor 3 (fgr3) polypeptide for use in the prevention or treatment of skeletal growth retardation disorders |
| JP2016510751A (ja) | 2013-03-06 | 2016-04-11 | ジェネンテック， インコーポレイテッド | 抗がん剤耐性を治療及び予防する方法 |
| TWI541022B (zh) | 2013-12-18 | 2016-07-11 | 應克隆公司 | 針對纖維母細胞生長因子受體－３（ｆｇｆｒ３）之化合物及治療方法 |
| CA2943355C (en) | 2014-03-25 | 2023-09-05 | Regeneron Pharmaceuticals, Inc. | Fgf21 receptor agonists and uses thereof |
| WO2015187521A2 (en) * | 2014-06-03 | 2015-12-10 | Merck Sharp & Dohme Corp. | Anti-blys antibodies |
| JP2017517552A (ja) | 2014-06-13 | 2017-06-29 | ジェネンテック， インコーポレイテッド | 抗癌剤耐性の治療及び防止方法 |
| CN107110932B (zh) * | 2014-09-05 | 2020-09-01 | 海珀菲纳研究股份有限公司 | 低场磁共振成像方法和设备 |
| AU2015321626B2 (en) | 2014-09-26 | 2021-12-16 | Janssen Pharmaceutica Nv | Use of FGFR mutant gene panels in identifying cancer patients that will be responsive to treatment with an FGFR inhibitor |
| WO2016134234A1 (en) * | 2015-02-19 | 2016-08-25 | Bioclin Therapeutics, Inc. | Methods, compositions, and kits for treatment of cancer |
| US20180237424A1 (en) | 2015-03-03 | 2018-08-23 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Fgfr3 antagonists |
| TW201711702A (zh) | 2015-06-04 | 2017-04-01 | 應克隆公司 | 使用針對纖維母細胞生長因子受體３（ｆｇｆｒ３）之化合物的療法 |
| WO2017100642A1 (en) | 2015-12-11 | 2017-06-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or preventing growth of tumors resistant to egfr and/or erbb3 blockade |
| CN109715658B (zh) | 2016-07-07 | 2023-09-12 | 辉瑞大药厂 | 可溶性成纤维细胞生长因子受体3(sfgfr3)多肽及其用途 |
| WO2018129451A2 (en) * | 2017-01-09 | 2018-07-12 | Merrimack Pharmaceuticals, Inc. | Anti-fgfr antibodies and methods of use |
| CA3189470A1 (en) | 2020-08-21 | 2022-02-24 | Yves SABBAGH | Fgfr3 antibodies and methods of use |
| CN114015770B (zh) * | 2021-12-30 | 2022-04-26 | 佛山市第三人民医院(佛山市精神卫生中心) | 精神分裂全外周血rna标志物fgfr3及其应用 |
| CN120500498A (zh) * | 2022-11-14 | 2025-08-15 | 瑞泽恩制药公司 | 用于成纤维细胞生长因子受体3介导的至星形胶质细胞的递送的组合物及方法 |
| AU2024207469A1 (en) | 2023-01-13 | 2025-08-28 | Regeneron Pharmaceuticals, Inc. | Fgfr3 binding molecules and methods of use thereof |
| WO2025240335A1 (en) | 2024-05-13 | 2025-11-20 | Regeneron Pharmaceuticals, Inc. | Fgfr3 binding molecules and methods of use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002102973A2 (en) * | 2001-06-20 | 2002-12-27 | Prochon Biotech Ltd. | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| WO2005066211A2 (en) * | 2003-12-19 | 2005-07-21 | Five Prime Therapeutics, Inc. | Fibroblast growth factor receptors 1, 2, 3, and 4 as targets for therapeutic intervention |
| US20100003258A1 (en) * | 2008-07-01 | 2010-01-07 | Zhigang Weng | Fibroblast growth factor receptor 3 (fgfr3) binding proteins |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| WO1988009344A1 (en) | 1987-05-21 | 1988-12-01 | Creative Biomolecules, Inc. | Targeted multifunctional proteins |
| KR20200058579A (ko) * | 2006-06-06 | 2020-05-27 | 얀센 백신스 앤드 프리벤션 비.브이. | 장내구균에 대한 사멸활성을 갖는 인간결합분자 및 그것의 용도 |
| HRP20130163T1 (hr) * | 2006-09-07 | 2013-03-31 | Crucell Holland B.V. | Ljudske molekule za vezanje koje mogu neutralizirati virus influence h5n1 i njihova uporaba |
| ES2453592T3 (es) * | 2007-08-02 | 2014-04-08 | Novimmune Sa | Anticuerpos anti-RANTES y métodos de uso de los mismos |
| EP3056513A1 (en) * | 2008-04-11 | 2016-08-17 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
| TWI381848B (zh) * | 2008-10-20 | 2013-01-11 | Imclone Llc | 抗纖維母細胞生長因子受體-3 (fgfr-3) 抗體及包含其之醫藥組合物 |
-
2009
- 2009-10-05 TW TW098133737A patent/TWI381848B/zh not_active IP Right Cessation
- 2009-10-05 AR ARP090103832A patent/AR073770A1/es unknown
- 2009-10-15 MX MX2011004317A patent/MX2011004317A/es active IP Right Grant
- 2009-10-15 EA EA201170590A patent/EA021584B1/ru not_active IP Right Cessation
- 2009-10-15 NZ NZ592369A patent/NZ592369A/xx not_active IP Right Cessation
- 2009-10-15 CA CA2741127A patent/CA2741127C/en not_active Expired - Fee Related
- 2009-10-15 KR KR1020117008935A patent/KR101370798B1/ko not_active Expired - Fee Related
- 2009-10-15 AU AU2009307841A patent/AU2009307841B2/en not_active Ceased
- 2009-10-15 WO PCT/US2009/060840 patent/WO2010048026A2/en not_active Ceased
- 2009-10-15 BR BRPI0919832A patent/BRPI0919832A8/pt not_active IP Right Cessation
- 2009-10-15 CN CN201310384769.3A patent/CN103524620A/zh active Pending
- 2009-10-15 UA UAA201104814A patent/UA101681C2/ru unknown
- 2009-10-15 JP JP2011532250A patent/JP5577345B2/ja not_active Expired - Fee Related
- 2009-10-15 US US12/579,825 patent/US8043618B2/en not_active Expired - Fee Related
- 2009-10-15 EP EP09737319A patent/EP2342232A2/en not_active Ceased
- 2009-10-15 CN CN200980141656.2A patent/CN102186884B/zh not_active Expired - Fee Related
-
2011
- 2011-03-14 ZA ZA2011/01938A patent/ZA201101938B/en unknown
- 2011-03-17 IL IL211807A patent/IL211807A0/en unknown
- 2011-09-19 US US13/235,900 patent/US8182815B2/en not_active Expired - Fee Related
-
2012
- 2012-04-20 US US13/452,043 patent/US8404240B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002102973A2 (en) * | 2001-06-20 | 2002-12-27 | Prochon Biotech Ltd. | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| WO2005066211A2 (en) * | 2003-12-19 | 2005-07-21 | Five Prime Therapeutics, Inc. | Fibroblast growth factor receptors 1, 2, 3, and 4 as targets for therapeutic intervention |
| US20100003258A1 (en) * | 2008-07-01 | 2010-01-07 | Zhigang Weng | Fibroblast growth factor receptor 3 (fgfr3) binding proteins |
Non-Patent Citations (8)
| Title |
|---|
| CHELLAIAH A. ET AL.: "MAPPING LIGAND BINDING DOMAINS IN CHIMERIC FIBROBLAST GROWTH FACTOR RECEPTOR MOLECULES". JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, INC, US LNKD- DOI:10.1074/JBC.274.49.34785, vol. 274, no. 49, 3 December 1999 (1999-12-03), pages 34785-34794, XP002951247, ISSN: 0021-9258 the whole document * |
| DVORAK P. ET AL.: "Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia". LEUKEMIA (BASINGSTOKE), vol. 17, no. 12, December 2003 (2003-12), pages 2418-2425, XP007913082, ISSN: 0887-6924, The whole document, in particular the methods; line 1 - page 2420, column 2, line 2 * |
| KEEGAN K. ET AL.: "ISOLATION OF AN ADDITIONAL MEMBER OF THE FIBROBLAST GROWTH FACTOR RECEPTOR FAMILY, FGFR-3" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES (PNAS), NATIONAL ACADEMY OF SCIENCE, US LNKD-DOI:10.1073/PNAS.88.4.1095, vol. 88, 1 February 1991 (1991-02-01), pages 1095-1099, XP002071229, ISSN: 0027-8424, the whole document * |
| MARTINEZ-TORRECUADRADA J. ET AL.: "Targeting the Extracellular Domain of Fibroblast Growth Factor Receptor 3 with Human Single-Chain Fv Antibodies Inhibits Bladder Carcinoma Cell Line Proliferation". CLINICAL CANCER RESEARCH, THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, US LNKD-DOI:10.1158/1078-0432.CCR-05-0282, vol. 11, no. 17, 1 September 2005 (2005-09-01), pages 6280-6290, XP003013913, ISSN: 1078-0432, cited in the application, the whole document * |
| RAUCHENBERGER R. ET AL.: "Human combinatorial Fab library yielding specific and functional antibodies against the human fibroblast growth factor receptor 3". JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, INC, US LNKD-DOI:10.1074/JBC.M303164200, vol. 278, no. 40, 3 July 2003 (2003-07-03), pages 38194-38205, XP002404703, ISSN: 0021-9258, the whole document * |
| SCOTET EMMANUEL ET AL.: "The choice between alternative IHb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific". BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1264, no. 2, 1995, pages 238-242, XP009133572, ISSN: 0006-3002, the whole document * |
| SUZANNE TRUDEL ET AL.: "The inhibitory anti-FGFR3 antibody, PRO-OOl, is cytotoxic to t(4;14) multiple myeloma cells". BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US LNKD- DOI:10.1182/BL00D-2005-10-4179, vol. 107, no. 10, 15 May 2006 (2006-05-15), pages 4039-4046, XP007913063, ISSN: 0006-4971, cited in the application, the whole document * |
| WANG W. ET AL.: "200 POSTER Transcriptome analysis method for in vivo mechanism of action study: IMC-DI1 anti-FGFR3 +/- cisplatin in bladder cancer models". EUROPEAN JOURNAL OF CANCER. SUPPLEMENT, PERGAMON, OXFORD, GB LNKD-DOI:10.1016/S1359-6349 (08)72132-3, vol. 6, no. 12, 1 October 2008 (2008-10-01), page 63, XP025534262, ISSN: 1359-6349 [retrieved on 2008-10-01], cited in the application, Abstract 200 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102186884B (zh) | 2014-08-13 |
| JP5577345B2 (ja) | 2014-08-20 |
| KR20110056554A (ko) | 2011-05-30 |
| US20100098696A1 (en) | 2010-04-22 |
| IL211807A0 (en) | 2011-06-30 |
| AU2009307841B2 (en) | 2013-09-12 |
| EP2342232A2 (en) | 2011-07-13 |
| CA2741127A1 (en) | 2010-04-29 |
| TW201026325A (en) | 2010-07-16 |
| EA201170590A1 (ru) | 2011-10-31 |
| WO2010048026A3 (en) | 2010-07-15 |
| US8182815B2 (en) | 2012-05-22 |
| BRPI0919832A2 (pt) | 2015-12-15 |
| US20120219563A1 (en) | 2012-08-30 |
| US8043618B2 (en) | 2011-10-25 |
| CN103524620A (zh) | 2014-01-22 |
| CN102186884A (zh) | 2011-09-14 |
| KR101370798B1 (ko) | 2014-03-14 |
| CA2741127C (en) | 2015-06-02 |
| WO2010048026A2 (en) | 2010-04-29 |
| US20120009200A1 (en) | 2012-01-12 |
| JP2012505912A (ja) | 2012-03-08 |
| NZ592369A (en) | 2013-02-22 |
| TWI381848B (zh) | 2013-01-11 |
| ZA201101938B (en) | 2012-08-29 |
| BRPI0919832A8 (pt) | 2019-01-08 |
| MX2011004317A (es) | 2011-06-24 |
| US8404240B2 (en) | 2013-03-26 |
| AR073770A1 (es) | 2010-12-01 |
| UA101681C2 (ru) | 2013-04-25 |
| AU2009307841A1 (en) | 2010-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA021584B1 (ru) | Ингибитор рецептора фактора роста фибробластов-3 (fgfr-3) и его применение | |
| JP7301106B2 (ja) | 線維芽増殖因子受容体２に対するモノクローナル抗体 | |
| US20250197526A1 (en) | Trispecific binding proteins and methods of use | |
| JP2022502371A (ja) | Ｄｌｌ３結合タンパク質および使用方法 | |
| US20120121505A1 (en) | Therapeutic compositions and methods | |
| KR20220144841A (ko) | Flt3 결합 단백질 및 사용 방법 | |
| KR20200042485A (ko) | EGFR 및 cMET에 결합하는 항체 | |
| JP6574257B2 (ja) | 新規の抗Ｎｏｄａｌ抗体及びその使用方法 | |
| KR20140125351A (ko) | 항-cd98 항체 및 이의 사용 방법 | |
| CN111848805B (zh) | 用于肿瘤免疫治疗的具有双Her2位点的双特异性抗体 | |
| KR102887692B1 (ko) | 항-bcam 항체 또는 그의 항원 결합 단편 | |
| CN109929036B (zh) | 一种表位特异的抗体筛选方法及所筛选到的抗体 | |
| CN112272564A (zh) | 可标靶vegfr2与vegfr3的双功能抗体 | |
| EP3082858B1 (en) | Adrenomedullin binder for use in therapy of cancer | |
| TW202330026A (zh) | 用於療法之抗btn3a活化抗體及il2促效劑之組合 | |
| KR20230158058A (ko) | 시알산-결합 ig-유사 렉틴 15에 특이적인 항체 및 이의 용도 | |
| KR20220048028A (ko) | 항-cd19 항체 및 그의 용도 | |
| KR20240149030A (ko) | 항-bcam 항체 및 항체-약물 접합체 | |
| CN118496364A (zh) | uPARAP特异性结合蛋白及其制备方法和应用 | |
| CN101356679A (zh) | 用于诊断和治疗癌症的组合物和方法 | |
| NZ626513B2 (en) | Anti-cd98 antibodies and methods of use thereof |
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 |
|
| 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): RU |