CZ303656B6 - Lécivo pro lécení ocního onemocnení - Google Patents
Lécivo pro lécení ocního onemocnení Download PDFInfo
- Publication number
- CZ303656B6 CZ303656B6 CZ20100386A CZ2010386A CZ303656B6 CZ 303656 B6 CZ303656 B6 CZ 303656B6 CZ 20100386 A CZ20100386 A CZ 20100386A CZ 2010386 A CZ2010386 A CZ 2010386A CZ 303656 B6 CZ303656 B6 CZ 303656B6
- Authority
- CZ
- Czechia
- Prior art keywords
- flt1
- vegf
- fit
- domain
- protein
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 9
- 208000030533 eye disease Diseases 0.000 title abstract description 3
- 101150048336 Flt1 gene Proteins 0.000 claims abstract description 224
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims abstract description 120
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract description 120
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 120
- 230000027455 binding Effects 0.000 claims abstract description 103
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 75
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 74
- 229920001184 polypeptide Polymers 0.000 claims abstract description 73
- 108091008605 VEGF receptors Proteins 0.000 claims abstract description 54
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims abstract description 51
- 230000004927 fusion Effects 0.000 claims abstract description 50
- 101150009958 FLT4 gene Proteins 0.000 claims abstract description 8
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 claims abstract description 8
- 230000008728 vascular permeability Effects 0.000 claims abstract description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 47
- 239000002773 nucleotide Substances 0.000 claims description 41
- 125000003729 nucleotide group Chemical group 0.000 claims description 41
- 108060003951 Immunoglobulin Proteins 0.000 claims description 7
- 102000018358 immunoglobulin Human genes 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 208000022873 Ocular disease Diseases 0.000 claims description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 3
- 230000002068 genetic effect Effects 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 abstract description 14
- 101150088608 Kdr gene Proteins 0.000 abstract description 11
- 230000001976 improved effect Effects 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 4
- 108020001507 fusion proteins Proteins 0.000 abstract 1
- 102000037865 fusion proteins Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 154
- 102000004169 proteins and genes Human genes 0.000 description 140
- 235000018102 proteins Nutrition 0.000 description 138
- 210000004027 cell Anatomy 0.000 description 95
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 85
- 102000058223 human VEGFA Human genes 0.000 description 85
- 102000005962 receptors Human genes 0.000 description 41
- 108020003175 receptors Proteins 0.000 description 41
- 235000001014 amino acid Nutrition 0.000 description 36
- 229940024606 amino acid Drugs 0.000 description 36
- 239000003446 ligand Substances 0.000 description 36
- 238000000034 method Methods 0.000 description 34
- 150000001413 amino acids Chemical class 0.000 description 32
- 241000699670 Mus sp. Species 0.000 description 30
- 238000003556 assay Methods 0.000 description 29
- 150000007523 nucleic acids Chemical class 0.000 description 25
- 238000002474 experimental method Methods 0.000 description 24
- 238000001542 size-exclusion chromatography Methods 0.000 description 24
- 230000021736 acetylation Effects 0.000 description 20
- 238000006640 acetylation reaction Methods 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 20
- 108020004414 DNA Proteins 0.000 description 19
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 18
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 17
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 16
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 16
- 210000002744 extracellular matrix Anatomy 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 16
- 108020004707 nucleic acids Proteins 0.000 description 16
- 102000039446 nucleic acids Human genes 0.000 description 16
- 239000013612 plasmid Substances 0.000 description 16
- 210000002966 serum Anatomy 0.000 description 16
- 238000002965 ELISA Methods 0.000 description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 14
- 230000003321 amplification Effects 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 238000003199 nucleic acid amplification method Methods 0.000 description 14
- 239000012634 fragment Substances 0.000 description 13
- 239000000499 gel Substances 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000013604 expression vector Substances 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 11
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 11
- 108010021466 Mutant Proteins Proteins 0.000 description 11
- 102000008300 Mutant Proteins Human genes 0.000 description 11
- 238000012217 deletion Methods 0.000 description 11
- 230000037430 deletion Effects 0.000 description 11
- 230000013595 glycosylation Effects 0.000 description 11
- 238000006206 glycosylation reaction Methods 0.000 description 11
- 230000003993 interaction Effects 0.000 description 11
- 108010082117 matrigel Proteins 0.000 description 11
- 230000006320 pegylation Effects 0.000 description 11
- 229920001223 polyethylene glycol Polymers 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000010276 construction Methods 0.000 description 10
- 235000018417 cysteine Nutrition 0.000 description 10
- 238000001514 detection method Methods 0.000 description 10
- 230000003834 intracellular effect Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 210000004291 uterus Anatomy 0.000 description 10
- 101100083342 Mus musculus Picalm gene Proteins 0.000 description 9
- 101100018718 Rattus norvegicus Il1rl1 gene Proteins 0.000 description 9
- 230000033115 angiogenesis Effects 0.000 description 9
- 150000001945 cysteines Chemical class 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 239000000186 progesterone Substances 0.000 description 9
- 229960003387 progesterone Drugs 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 230000000903 blocking effect Effects 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 102000000844 Cell Surface Receptors Human genes 0.000 description 7
- 108010001857 Cell Surface Receptors Proteins 0.000 description 7
- 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 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 7
- 210000004246 corpus luteum Anatomy 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000013613 expression plasmid Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 108091008146 restriction endonucleases Proteins 0.000 description 7
- 238000012286 ELISA Assay Methods 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 238000010254 subcutaneous injection Methods 0.000 description 6
- 239000007929 subcutaneous injection Substances 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 230000004988 N-glycosylation Effects 0.000 description 5
- 108010025020 Nerve Growth Factor Proteins 0.000 description 5
- 238000012408 PCR amplification Methods 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 238000000149 argon plasma sintering Methods 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- 235000018977 lysine Nutrition 0.000 description 5
- 210000004088 microvessel Anatomy 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 206010003445 Ascites Diseases 0.000 description 4
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 206010018338 Glioma Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 4
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 4
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 4
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 4
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 4
- 208000032594 Vascular Remodeling Diseases 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000012345 acetylating agent Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000001823 molecular biology technique Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- 230000016087 ovulation Effects 0.000 description 4
- 238000012510 peptide mapping method Methods 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000001850 reproductive effect Effects 0.000 description 4
- 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 4
- 239000000725 suspension Substances 0.000 description 4
- 238000004114 suspension culture Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- 208000032612 Glial tumor Diseases 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 101150056950 Ntrk2 gene Proteins 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 229960000723 ampicillin Drugs 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 235000009697 arginine Nutrition 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 108091005573 modified proteins Proteins 0.000 description 3
- 102000035118 modified proteins Human genes 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 238000011533 pre-incubation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000002993 trophoblast Anatomy 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 210000003556 vascular endothelial cell Anatomy 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- 210000000264 venule Anatomy 0.000 description 3
- MDUQWFYJHRLNRN-UHFFFAOYSA-N 1-acetyloxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound CC(=O)ON1C(=O)CC(S(O)(=O)=O)C1=O MDUQWFYJHRLNRN-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010048962 Brain oedema Diseases 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 101100445049 Caenorhabditis elegans elt-1 gene Proteins 0.000 description 2
- 238000007900 DNA-DNA hybridization Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 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
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 102400001270 Neuronostatin Human genes 0.000 description 2
- 108090000742 Neurotrophin 3 Proteins 0.000 description 2
- 102100029268 Neurotrophin-3 Human genes 0.000 description 2
- 108090000099 Neurotrophin-4 Proteins 0.000 description 2
- 102100033857 Neurotrophin-4 Human genes 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 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 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 101100310691 Rattus norvegicus Spata6 gene Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000012505 Superdex™ Substances 0.000 description 2
- 102100033130 T-box transcription factor T Human genes 0.000 description 2
- 101710086566 T-box transcription factor T Proteins 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 241000545067 Venus Species 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 208000037883 airway inflammation Diseases 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 208000006752 brain edema Diseases 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- 125000002228 disulfide group Chemical group 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 210000003989 endothelium vascular Anatomy 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 108020001756 ligand binding domains Proteins 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- SXTAYKAGBXMACB-UHFFFAOYSA-N methionine sulfoximine Chemical compound CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 229940032018 neurotrophin 3 Drugs 0.000 description 2
- 229920002113 octoxynol Polymers 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 108010079892 phosphoglycerol kinase Proteins 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
- 230000003169 placental effect Effects 0.000 description 2
- -1 polyethylene Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000008719 thickening Effects 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
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000003120 Angiofibroma Diseases 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- GIVATXIGCXFQQA-FXQIFTODSA-N Arg-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N GIVATXIGCXFQQA-FXQIFTODSA-N 0.000 description 1
- XWGJDUSDTRPQRK-ZLUOBGJFSA-N Asn-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O XWGJDUSDTRPQRK-ZLUOBGJFSA-N 0.000 description 1
- HCZQKHSRYHCPSD-IUKAMOBKSA-N Asn-Thr-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HCZQKHSRYHCPSD-IUKAMOBKSA-N 0.000 description 1
- LIVXPXUVXFRWNY-CIUDSAMLSA-N Asp-Lys-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O LIVXPXUVXFRWNY-CIUDSAMLSA-N 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 101100025206 Chlamydomonas reinhardtii Mut11 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 102000016989 Ciliary Neurotrophic Factor Receptor Human genes 0.000 description 1
- 108010000063 Ciliary Neurotrophic Factor Receptor Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102100030323 Epigen Human genes 0.000 description 1
- 108010016906 Epigen Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010001515 Galectin 4 Proteins 0.000 description 1
- 102100039556 Galectin-4 Human genes 0.000 description 1
- 206010018092 Generalised oedema Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- BFEZQZKEPRKKHV-SRVKXCTJSA-N Glu-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCCCN)C(=O)O BFEZQZKEPRKKHV-SRVKXCTJSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- VXKCPBPQEKKERH-IUCAKERBSA-N Gly-Arg-Pro Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N1CCC[C@H]1C(O)=O VXKCPBPQEKKERH-IUCAKERBSA-N 0.000 description 1
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 1
- NSVOVKWEKGEOQB-LURJTMIESA-N Gly-Pro-Gly Chemical compound NCC(=O)N1CCC[C@H]1C(=O)NCC(O)=O NSVOVKWEKGEOQB-LURJTMIESA-N 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- LLZLRXBTOOFODM-QSFUFRPTSA-N Ile-Asp-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N LLZLRXBTOOFODM-QSFUFRPTSA-N 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102000003683 Neurotrophin-4 Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 102100038551 Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108010089814 Plant Lectins Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 101100496572 Rattus norvegicus C6 gene Proteins 0.000 description 1
- 101000852966 Rattus norvegicus Interleukin-1 receptor-like 1 Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- BTPAWKABYQMKKN-LKXGYXEUSA-N Ser-Asp-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BTPAWKABYQMKKN-LKXGYXEUSA-N 0.000 description 1
- WOUIMBGNEUWXQG-VKHMYHEASA-N Ser-Gly Chemical compound OC[C@H](N)C(=O)NCC(O)=O WOUIMBGNEUWXQG-VKHMYHEASA-N 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 102100038126 Tenascin Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 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
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 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 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 201000003511 ectopic pregnancy Diseases 0.000 description 1
- 230000032692 embryo implantation Effects 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000004996 female reproductive system Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- 239000012537 formulation buffer Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000000938 luteal effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 201000003142 neovascular glaucoma Diseases 0.000 description 1
- 229940097998 neurotrophin 4 Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 108040002068 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity proteins Proteins 0.000 description 1
- 210000002856 peripheral neuron Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 230000028742 placenta development Effects 0.000 description 1
- 239000003726 plant lectin Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 230000006259 progesterone secretion Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000018448 secretion by cell Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000010512 small scale reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001361 thrombopoietic effect Effects 0.000 description 1
- 230000036964 tight binding Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 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
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 102000015534 trkB Receptor Human genes 0.000 description 1
- 108010064880 trkB Receptor Proteins 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 230000006492 vascular dysfunction Effects 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Dermatology (AREA)
- Biotechnology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13813399P | 1999-06-08 | 1999-06-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ303656B6 true CZ303656B6 (cs) | 2013-01-30 |
Family
ID=22480568
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20100386A CZ303656B6 (cs) | 1999-06-08 | 2000-05-23 | Lécivo pro lécení ocního onemocnení |
| CZ20014387A CZ302689B6 (cs) | 1999-06-08 | 2000-05-23 | Izolovaná molekula nukleové kyseliny, fúzní polypeptid jí kódovaný, vektor s jejím obsahem, systém vektor-hostitel pro produkci fúzního polypeptidu a zpusob jeho prípravy, antagonista dimerního VEGF a použití |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20014387A CZ302689B6 (cs) | 1999-06-08 | 2000-05-23 | Izolovaná molekula nukleové kyseliny, fúzní polypeptid jí kódovaný, vektor s jejím obsahem, systém vektor-hostitel pro produkci fúzního polypeptidu a zpusob jeho prípravy, antagonista dimerního VEGF a použití |
Country Status (32)
| Country | Link |
|---|---|
| EP (2) | EP1544299B1 (enExample) |
| JP (2) | JP4723140B2 (enExample) |
| KR (1) | KR100659477B1 (enExample) |
| CN (3) | CN103349781B (enExample) |
| AT (2) | ATE293164T1 (enExample) |
| AU (2) | AU779303B2 (enExample) |
| BE (1) | BE2013C029I2 (enExample) |
| BR (2) | BR0011407A (enExample) |
| CA (1) | CA2376379C (enExample) |
| CY (2) | CY1108883T1 (enExample) |
| CZ (2) | CZ303656B6 (enExample) |
| DE (2) | DE60019415T2 (enExample) |
| DK (2) | DK1183353T3 (enExample) |
| ES (2) | ES2319305T3 (enExample) |
| FR (1) | FR13C0028I2 (enExample) |
| HR (1) | HRP20010908B1 (enExample) |
| HU (3) | HU229156B1 (enExample) |
| IL (3) | IL146890A0 (enExample) |
| LT (1) | LTC1183353I2 (enExample) |
| LU (1) | LU92195I2 (enExample) |
| ME (2) | ME00024B (enExample) |
| MX (1) | MXPA01012630A (enExample) |
| NO (4) | NO330775B1 (enExample) |
| NZ (1) | NZ515913A (enExample) |
| PL (1) | PL208247B1 (enExample) |
| PT (2) | PT1544299E (enExample) |
| RS (1) | RS50073B (enExample) |
| RU (1) | RU2265661C2 (enExample) |
| SK (1) | SK287332B6 (enExample) |
| UA (1) | UA74146C2 (enExample) |
| WO (1) | WO2000075319A1 (enExample) |
| ZA (1) | ZA200110068B (enExample) |
Families Citing this family (106)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6710174B2 (en) | 2001-09-13 | 2004-03-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of vascular endothelial growth factor receptor-1 expression |
| US6100071A (en) | 1996-05-07 | 2000-08-08 | Genentech, Inc. | Receptors as novel inhibitors of vascular endothelial growth factor activity and processes for their production |
| US7087411B2 (en) * | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
| US6833349B2 (en) * | 1999-06-08 | 2004-12-21 | Regeneron Pharmaceuticals, Inc. | Methods of treating inflammatory skin diseases |
| US7396664B2 (en) | 1999-06-08 | 2008-07-08 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
| JP4669984B2 (ja) | 2001-01-19 | 2011-04-13 | ベジェニクス リミテッド | 腫瘍画像化のターゲットとしてのＦ１ｔ４（ＶＥＧＦＲ−３）および抗腫瘍療法 |
| US6734017B2 (en) | 2001-09-28 | 2004-05-11 | Isis Pharmaceuticals, Inc. | Antisense modulation of vascular endothelial growth factor receptor-2 expression |
| ES2362648T3 (es) | 2002-05-04 | 2011-07-08 | Acorda Therapeutics, Inc. | Composiciones y métodos para promover la proyección neuronal. |
| DK1608685T3 (da) | 2003-03-28 | 2007-06-11 | Regeneron Pharma | VEGF antagonister til behandlingen af diabetes |
| EP3211084B1 (en) | 2003-05-16 | 2019-03-27 | Acorda Therapeutics, Inc. | Proteoglycan degrading mutants for treatment of cns |
| JP5399612B2 (ja) * | 2003-05-16 | 2014-01-29 | アコーダ セラピューティクス、インク． | Ｃｎｓを治療するための融合タンパク質 |
| US7959914B2 (en) | 2003-05-16 | 2011-06-14 | Acorda Therapeutics, Inc. | Methods of reducing extravasation of inflammatory cells |
| WO2004106378A2 (en) * | 2003-05-28 | 2004-12-09 | Regeneron Pharmaceuticals, Inc. | Method of treating corneal transplant rejection by using vegf antagonists |
| US7186699B2 (en) | 2003-06-03 | 2007-03-06 | Cell Genesys, Inc. | Method for treating cancer by vector-mediated delivery of one or more anti-angiogenic or pro-apoptotic genes |
| WO2004110490A2 (en) * | 2003-06-06 | 2004-12-23 | Regeneron Pharmaceuticals, Inc. | Use of vegf inhibitors for tumor regression |
| US7399612B2 (en) | 2003-06-30 | 2008-07-15 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
| AR046510A1 (es) * | 2003-07-25 | 2005-12-14 | Regeneron Pharma | Composicion de un antagonista de vegf y un agente anti-proliferativo |
| US20050112061A1 (en) * | 2003-08-06 | 2005-05-26 | Jocelyn Holash | Use of a VEGF antagonist in combination with radiation therapy |
| AU2005244933B2 (en) | 2004-05-18 | 2011-08-04 | Acorda Therapeutics, Inc. | Methods of purifying chondroitinase and stable formulations thereof |
| DK1767546T3 (da) | 2004-06-08 | 2012-04-23 | Chengdu Kanghong Biotechnologies Co Ltd | Angiogenese-inhiberende kimært protein og dets anvendelse |
| MXPA06014421A (es) | 2004-06-10 | 2007-05-04 | Regeneron Pharma | Uso de inhibidores de vegf para el tratamiento de cancer humano. |
| CN1968709A (zh) * | 2004-06-18 | 2007-05-23 | 瑞泽恩制药公司 | 用于治疗恶性胸腔积液的vegf抑制剂 |
| CN1997386B (zh) | 2004-07-30 | 2012-05-30 | 瑞泽恩制药公司 | 通过阻断vegf介导的活性来治疗i型糖尿病的方法 |
| EP1804835B9 (en) * | 2004-09-13 | 2010-09-29 | Genzyme Corporation | Multimeric constructs |
| FR2878749B1 (fr) * | 2004-12-03 | 2007-12-21 | Aventis Pharma Sa | Combinaisons antitumorales contenant en agent inhibiteur de vegt et du 5fu ou un de ses derives |
| CA2621047A1 (en) | 2005-02-02 | 2006-08-24 | Regeneron Pharmaceuticals, Inc. | Method of treating eye injury with local administration of a vegf inhibitor |
| US20060217311A1 (en) | 2005-03-25 | 2006-09-28 | Daniel Dix | VEGF antagonist formulations |
| JP5189985B2 (ja) | 2005-09-26 | 2013-04-24 | アコーダ セラピューティクス、インク． | コンドロイチナーゼａｂｃｉ変異体を用いた組成物およびその使用方法 |
| CA2630839C (en) † | 2005-12-16 | 2017-01-17 | Regeneron Pharmaceuticals, Inc. | Therapeutic methods for inhibiting tumor growth with dll4 antagonists |
| FR2895258B1 (fr) | 2005-12-22 | 2008-03-21 | Aventis Pharma Sa | Combinaison comprenant de la combretastatine et des agents anticancereux |
| US8216575B2 (en) | 2006-03-31 | 2012-07-10 | Chengdu Kanghong Biotechnologies Co., Ltd. | Inhibition of neovascularization with a soluble chimeric protein comprising VEGF FLT-1 and KDR domains |
| CN100502945C (zh) * | 2006-03-31 | 2009-06-24 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在治疗眼睛疾病中的应用 |
| PT2944306T (pt) | 2006-06-16 | 2021-02-15 | Regeneron Pharma | Formulações antagonistas de vegf adequadas para administração intravitreal |
| HUE028379T2 (en) | 2006-09-29 | 2016-12-28 | Oncomed Pharm Inc | Preparations and procedures for the diagnosis and treatment of cancer |
| CA3086902C (en) | 2006-10-10 | 2021-11-09 | Acorda Therapeutics, Inc. | Compositions and methods of using chondroitinase abci mutants |
| FR2918279B1 (fr) * | 2007-07-05 | 2010-10-22 | Aventis Pharma Sa | Combinaisons antitumorales contenant un agent inhibiteur de vegf et de l'irinotecan |
| CN101575379B (zh) * | 2008-05-09 | 2012-05-30 | 上海抗体药物国家工程研究中心有限公司 | 可溶性vegfr双功能融合受体、其制备方法及用途 |
| ES2836948T3 (es) | 2008-11-03 | 2021-06-28 | Molecular Partners Ag | Proteínas de unión que inhiben la interacción del receptor de VEGF-A |
| CN101838329A (zh) * | 2009-03-18 | 2010-09-22 | 嘉和生物药业有限公司 | 抗血管新生融合蛋白 |
| TR201818814T4 (tr) | 2009-10-16 | 2019-01-21 | Oncomed Pharm Inc | Dll4 antagonist antikorlarının ve anti-hipertansif ajanların terapötik kombinasyonu ve kullanımı. |
| TWI510246B (zh) | 2010-04-30 | 2015-12-01 | Molecular Partners Ag | 抑制ｖｅｇｆ－ａ受體交互作用的經修飾結合性蛋白質 |
| ES2652508T3 (es) | 2010-08-06 | 2018-02-02 | Genzyme Corporation | Composiciones de antagonistas de VEGF y sus usos |
| US20140080153A1 (en) * | 2011-01-07 | 2014-03-20 | Chugai Seiyaku Kabushiki Kaisha | Method for improving physical properties of antibody |
| EP3763379A1 (en) | 2011-01-13 | 2021-01-13 | Regeneron Pharmaceuticals, Inc. | Use of a vegf antagonist to treat angiogenic eye disorders |
| JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
| KR101397088B1 (ko) | 2011-06-10 | 2014-05-19 | 강원대학교산학협력단 | 암세포 증식 억제와 혈관신생 억제를 위한 융합 단백질 및 이를 포함한 항암 조성물 |
| JO3370B1 (ar) * | 2011-11-10 | 2019-03-13 | Regeneron Pharma | طريقة لتثبيط نمو الورم عن طريق تثبيط مستقبل انترلوكين 6 |
| JP6138815B2 (ja) * | 2011-12-01 | 2017-05-31 | エーピー バイオサイエンシーズ， インコーポレイテッド | 補体経路およびｖｅｇｆ経路に対するタンパク質インヒビターおよびそれらの使用方法 |
| CN103304668B (zh) * | 2012-03-12 | 2015-10-28 | 江苏健德生物药业有限公司 | Ultra-VEGF-trap免疫融合蛋白、其制备方法及其应用 |
| PL2846836T3 (pl) | 2012-05-07 | 2020-01-31 | Allergan, Inc. | Sposób leczenia amd u pacjentów opornych na terapię anty- vegf |
| WO2014006113A1 (en) | 2012-07-03 | 2014-01-09 | Sanofi | Method of treating cancer by effective amounts of aflibercept |
| TW201438736A (zh) | 2012-11-14 | 2014-10-16 | Regeneron Pharma | 以ｄｌｌ４拮抗劑治療卵巢癌之方法 |
| HUE048687T2 (hu) | 2013-02-18 | 2020-08-28 | Vegenics Pty Ltd | Ligandum kötõ molekulák és alkalmazásaik |
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| CN104193828B (zh) * | 2013-09-12 | 2017-04-05 | 北京韩美药品有限公司 | 同时阻断her2和vegfr信号通路的重组融合蛋白 |
| CN105960247A (zh) | 2013-11-05 | 2016-09-21 | 阿勒根公司 | 用抗vegf darpin治疗眼病的方法 |
| CA2947456C (en) | 2014-05-12 | 2023-03-14 | Formycon Ag | Pre-filled plastic syringe containing a vegf antagonist |
| MX375557B (es) | 2014-07-18 | 2025-03-06 | Sanofi Sa | Método para predecir el resultado de un tratamiento con aflibercept de un paciente que se sospecha que padece un cáncer. |
| JP2016036322A (ja) * | 2014-08-11 | 2016-03-22 | 日本化薬株式会社 | 血管新生因子と結合するキメラタンパク質 |
| CA2970315C (en) | 2014-12-11 | 2023-08-22 | Bayer Healthcare Llc | Use of anti-vegf agents to treat lesions in macular degeneration patients |
| GB201503453D0 (en) | 2015-03-01 | 2015-04-15 | Jain Arjun | Endothelin-1"sponge" |
| TWI870789B (zh) | 2015-08-04 | 2025-01-21 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
| WO2017046140A1 (en) | 2015-09-18 | 2017-03-23 | Bayer Pharma Aktiengesellschaft | Treatment regimens for dr and rvo in dependence of the extent of retinal ischemia |
| WO2017065559A1 (ko) | 2015-10-15 | 2017-04-20 | (주)알테오젠 | Igg fc 도메인을 가지는 융합 단백질의 생산방법 |
| KR101936049B1 (ko) * | 2015-10-15 | 2019-01-08 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 생산방법 |
| KR102854749B1 (ko) | 2015-11-18 | 2025-09-04 | 에스아이오2 메디컬 프로덕츠, 엘엘씨 | 안과 제제용 제약 패키지 |
| MX2018006171A (es) | 2015-11-18 | 2018-12-19 | Formycon Ag | Jeringa de plastico precargada que contiene un antagonista de vegf. |
| EP4556023A3 (en) | 2015-11-18 | 2025-10-15 | Formycon AG | Pre-filled pharmaceutical package comprising a liquid formulation of a vegf-antagonist |
| WO2017084616A1 (en) * | 2015-11-19 | 2017-05-26 | Zhuhai Tairuishang Biopharm Ltd. | Methods and compositions for binding vegf |
| KR102261636B1 (ko) | 2015-12-03 | 2021-06-07 | 리제너론 파마슈티칼스 인코포레이티드 | 항-vegf로 치료된 연령-관련 황반 변성을 앓고 있는 환자에서의 임상 결과와 유전적 변이체를 연관시키는 방법 |
| US10576128B2 (en) | 2016-01-26 | 2020-03-03 | Formycon Ag | Liquid formulation of a VEGF antagonist |
| JPWO2018070390A1 (ja) | 2016-10-12 | 2019-08-22 | 第一三共株式会社 | 抗ｒｏｂｏ４抗体と他剤を含む組成物 |
| US11135266B2 (en) | 2016-11-21 | 2021-10-05 | Just-Evotec Biologics, Inc. | Aflibercept formulations and uses thereof |
| WO2018215580A1 (en) | 2017-05-24 | 2018-11-29 | Formycon Ag | Method for sterilizing prefilled plastic syringes containing a vegf antagonist |
| US20200237997A1 (en) | 2017-05-24 | 2020-07-30 | Formycon Ag | Sterilizable pre-filled pharmaceutical packages comprising a liquid formulation of a vegf-antagonist |
| CA3063995A1 (en) | 2017-05-24 | 2018-11-29 | Sio2 Medical Products, Inc. | Sterilizable pharmaceutical package for ophthalmic formulations |
| TW201904610A (zh) | 2017-06-14 | 2019-02-01 | 德商拜耳製藥公司 | 用於治療新生血管型青光眼之非抗體vegf拮抗劑 |
| WO2019020777A1 (en) | 2017-07-26 | 2019-01-31 | Formycon Ag | LIQUID FORMULATION OF A VEGF ANTAGONIST |
| CN111344410B (zh) | 2017-08-17 | 2023-09-15 | 济世易为生物有限公司 | 从宿主细胞半乳糖凝集素和其他污染物中纯化糖基化蛋白的方法 |
| MY202872A (en) | 2017-11-20 | 2024-05-28 | Just Evotec Biologics Inc | Aflibercept formulations containing a lysine salt as tonicifying agent and uses thereof |
| CR20200282A (es) | 2017-11-27 | 2021-02-18 | 4D Molecular Therapeutics Inc | Cápsides variantes de virus adenoasociados y su uso para inhibir la angiogénesis |
| CN111465407A (zh) | 2017-11-30 | 2020-07-28 | 瑞泽恩制药公司 | 使用vegf拮抗剂治疗生血管性眼病 |
| AU2018385394B2 (en) * | 2017-12-13 | 2024-05-02 | Regeneron Pharmaceuticals, Inc. | Devices and systems for chromatography column bed support management and related methods |
| BR112020015074A2 (pt) * | 2018-01-26 | 2020-12-08 | The Regents Of The University Of California | Métodos e composições para tratamento de transtornos angiogênicos com uso de agentes anti-vegf |
| BR112020017872A2 (pt) | 2018-03-02 | 2020-12-22 | Kodiak Sciences Inc. | Anticorpos de il-6 e construtos de fusão e conjugados dos mesmos |
| JOP20200275A1 (ar) | 2018-05-10 | 2020-11-02 | Regeneron Pharma | صيغ تحتوي على بروتين اندماج لمستقبلvegf مرتفعة التركيز |
| TW202016125A (zh) * | 2018-05-10 | 2020-05-01 | 美商再生元醫藥公司 | 用於定量及調節蛋白質黏度之系統與方法 |
| US11519020B2 (en) | 2018-05-25 | 2022-12-06 | Regeneron Pharmaceuticals, Inc. | Methods of associating genetic variants with a clinical outcome in patients suffering from age-related macular degeneration treated with anti-VEGF |
| CN111378044B (zh) | 2018-12-28 | 2022-07-15 | 长春金赛药业有限责任公司 | 抗体融合蛋白、制备方法及其应用 |
| WO2020229584A1 (en) | 2019-05-16 | 2020-11-19 | Formycon Ag | Method for reducing methionine oxidation in recombinant proteins |
| JP2022546082A (ja) | 2019-09-03 | 2022-11-02 | アムジエン・インコーポレーテツド | 薬物送達のための注入デバイス及び注入デバイスのためのパッケージ |
| AU2020348947B2 (en) | 2019-09-16 | 2025-11-27 | Amgen Inc. | Method for external sterilization of drug delivery device |
| CA3157509A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
| CA3168512A1 (en) | 2019-11-25 | 2021-06-03 | Napoleone Ferrara | Long-acting vegf inhibitors for intraocular neovascularization |
| MY193353A (en) * | 2019-12-06 | 2022-10-06 | Regeneron Pharma | Anti-vegf protein compositions and methods for producing the same |
| MX2022006751A (es) | 2019-12-06 | 2022-08-19 | Regeneron Pharma | Minitrampas de vegf y metodos de uso de las mismas. |
| MX2022010177A (es) | 2020-02-24 | 2022-09-12 | Amgen Inc | Envases y sistemas para su uso durante la esterilizacion externa de dispositivos de administracion de farmacos. |
| CN115803009A (zh) | 2020-05-08 | 2023-03-14 | 瑞泽恩制药公司 | 用于治疗眼病和癌症的vegf阱和微阱及方法 |
| WO2022231930A1 (en) | 2021-04-26 | 2022-11-03 | Celanese Eva Performance Polymers Llc | Implantable device for sustained release of a macromolecular drug compound |
| EP4145456A1 (en) | 2021-09-06 | 2023-03-08 | Bayer AG | Prediction of a change related to a macular fluid |
| WO2023092324A1 (zh) | 2021-11-24 | 2023-06-01 | 苏州光度生物科技有限公司 | 多特异性配体结合分子及其应用 |
| KR102764987B1 (ko) | 2022-08-02 | 2025-02-12 | 주식회사 파노로스바이오사이언스 | 변형된 융합 단백질 및 이의 용도 |
| KR20250065646A (ko) | 2022-09-16 | 2025-05-13 | 치루 파머수티컬 컴퍼니 리미티드 | 안정적인 고농도 자가완충식 약물 조성물 |
| WO2025033876A1 (ko) * | 2023-08-04 | 2025-02-13 | 주식회사 파노로스바이오사이언스 | 변형된 융합 단백질과 scFv의 결합체 및 이의 용도 |
| WO2025213011A1 (en) | 2024-04-05 | 2025-10-09 | Amgen Inc. | Method of assessing stopper movement in a drug delivery device |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997044453A1 (en) * | 1996-05-07 | 1997-11-27 | Genentech, Inc. | Novel inhibitors of vascular endothelial growth factor activity, their uses and processes for their production |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9506466D0 (en) * | 1994-08-26 | 1995-05-17 | Prolifix Ltd | Cell cycle regulated repressor and dna element |
-
2000
- 2000-05-23 DK DK00932721T patent/DK1183353T3/da active
- 2000-05-23 SK SK1752-2001A patent/SK287332B6/sk not_active IP Right Cessation
- 2000-05-23 NZ NZ515913A patent/NZ515913A/xx not_active IP Right Cessation
- 2000-05-23 BR BR0011407-3A patent/BR0011407A/pt not_active IP Right Cessation
- 2000-05-23 CN CN201310118971.1A patent/CN103349781B/zh not_active Expired - Lifetime
- 2000-05-23 PL PL352246A patent/PL208247B1/pl active Protection Beyond IP Right Term
- 2000-05-23 CN CNB008115443A patent/CN100523187C/zh not_active Expired - Lifetime
- 2000-05-23 BR BRPI0011407A patent/BRPI0011407B8/pt unknown
- 2000-05-23 UA UA2001128378A patent/UA74146C2/uk unknown
- 2000-05-23 CZ CZ20100386A patent/CZ303656B6/cs not_active IP Right Cessation
- 2000-05-23 ES ES05001328T patent/ES2319305T3/es not_active Expired - Lifetime
- 2000-05-23 RU RU2002100071/13A patent/RU2265661C2/ru active Protection Beyond IP Right Term
- 2000-05-23 CN CN2008101093559A patent/CN101433715B/zh not_active Expired - Lifetime
- 2000-05-23 RS YUP-869/01A patent/RS50073B/sr unknown
- 2000-05-23 EP EP05001328A patent/EP1544299B1/en not_active Expired - Lifetime
- 2000-05-23 DE DE60019415T patent/DE60019415T2/de not_active Expired - Lifetime
- 2000-05-23 ME MEP-2008-32A patent/ME00024B/me unknown
- 2000-05-23 AU AU50404/00A patent/AU779303B2/en not_active Expired
- 2000-05-23 HU HU0201515A patent/HU229156B1/hu active Protection Beyond IP Right Term
- 2000-05-23 IL IL14689000A patent/IL146890A0/xx unknown
- 2000-05-23 HR HR20010908A patent/HRP20010908B1/xx not_active IP Right Cessation
- 2000-05-23 PT PT05001328T patent/PT1544299E/pt unknown
- 2000-05-23 AT AT00932721T patent/ATE293164T1/de active
- 2000-05-23 MX MXPA01012630A patent/MXPA01012630A/es active IP Right Grant
- 2000-05-23 DK DK05001328T patent/DK1544299T3/da active
- 2000-05-23 EP EP00932721A patent/EP1183353B1/en not_active Expired - Lifetime
- 2000-05-23 PT PT00932721T patent/PT1183353E/pt unknown
- 2000-05-23 ES ES00932721T patent/ES2237429T3/es not_active Expired - Lifetime
- 2000-05-23 ME MEP-32/08A patent/MEP3208A/xx unknown
- 2000-05-23 DE DE60041159T patent/DE60041159D1/de not_active Expired - Lifetime
- 2000-05-23 JP JP2001502582A patent/JP4723140B2/ja not_active Expired - Lifetime
- 2000-05-23 WO PCT/US2000/014142 patent/WO2000075319A1/en not_active Ceased
- 2000-05-23 KR KR1020017015839A patent/KR100659477B1/ko not_active Expired - Lifetime
- 2000-05-23 AT AT05001328T patent/ATE417928T1/de active
- 2000-05-23 CZ CZ20014387A patent/CZ302689B6/cs not_active IP Right Cessation
- 2000-05-23 CA CA002376379A patent/CA2376379C/en not_active Expired - Lifetime
- 2000-05-23 HU HU1300086A patent/HU230159B1/hu unknown
-
2001
- 2001-12-03 IL IL146890A patent/IL146890A/en active Protection Beyond IP Right Term
- 2001-12-06 ZA ZA200110068A patent/ZA200110068B/xx unknown
- 2001-12-10 NO NO20016036A patent/NO330775B1/no active Protection Beyond IP Right Term
-
2005
- 2005-03-31 AU AU2005201365A patent/AU2005201365B2/en not_active Expired
-
2008
- 2008-03-17 IL IL190234A patent/IL190234A0/en not_active IP Right Cessation
-
2009
- 2009-03-16 CY CY20091100288T patent/CY1108883T1/el unknown
-
2010
- 2010-05-06 NO NO20100656A patent/NO332559B1/no not_active IP Right Cessation
- 2010-10-06 JP JP2010226970A patent/JP5273746B2/ja not_active Expired - Lifetime
-
2013
- 2013-05-13 CY CY2013019C patent/CY2013019I2/el unknown
- 2013-05-13 BE BE2013C029C patent/BE2013C029I2/fr unknown
- 2013-05-14 LT LTPA2013009C patent/LTC1183353I2/lt unknown
- 2013-05-14 LU LU92195C patent/LU92195I2/fr unknown
- 2013-05-14 FR FR13C0028C patent/FR13C0028I2/fr active Active
- 2013-05-15 NO NO2013010C patent/NO2013010I1/no unknown
- 2013-09-17 HU HUS1300052C patent/HUS1300052I1/hu unknown
-
2022
- 2022-12-21 NO NO2022060C patent/NO2022060I1/no unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997044453A1 (en) * | 1996-05-07 | 1997-11-27 | Genentech, Inc. | Novel inhibitors of vascular endothelial growth factor activity, their uses and processes for their production |
Non-Patent Citations (1)
| Title |
|---|
| Davis-Smyth T. et al.: "The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade", EMBO Journal, Vol. 15(18), 4919-4927, 1996 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7964377B2 (en) | Nucleic acid molecule encoding a fusion polypeptide capable of binding VEGF | |
| CZ303656B6 (cs) | Lécivo pro lécení ocního onemocnení | |
| CA2588221C (en) | Modified chimeric polypeptides with improved pharmacokinetic properties | |
| HK1043388B (en) | Modified chimeric polypeptides with improved pharmacokinetic properties |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4A | Patent expired |
Effective date: 20200523 |