ES2836948T3 - Proteínas de unión que inhiben la interacción del receptor de VEGF-A - Google Patents
Proteínas de unión que inhiben la interacción del receptor de VEGF-A Download PDFInfo
- Publication number
- ES2836948T3 ES2836948T3 ES09756279T ES09756279T ES2836948T3 ES 2836948 T3 ES2836948 T3 ES 2836948T3 ES 09756279 T ES09756279 T ES 09756279T ES 09756279 T ES09756279 T ES 09756279T ES 2836948 T3 ES2836948 T3 ES 2836948T3
- Authority
- ES
- Spain
- Prior art keywords
- amino acid
- acid residue
- group
- vegf
- binding protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108091008324 binding proteins Proteins 0.000 title claims abstract description 133
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 title description 24
- 230000010799 Receptor Interactions Effects 0.000 title description 2
- 102000014914 Carrier Proteins Human genes 0.000 title 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 title 1
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 148
- 102000023732 binding proteins Human genes 0.000 claims abstract description 132
- 230000027455 binding Effects 0.000 claims abstract description 117
- 108010049777 Ankyrins Proteins 0.000 claims abstract description 116
- 102000008102 Ankyrins Human genes 0.000 claims abstract description 116
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 37
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 34
- 229910052720 vanadium Inorganic materials 0.000 claims abstract description 34
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 28
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims abstract description 25
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 18
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 5
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims description 78
- 102000004169 proteins and genes Human genes 0.000 claims description 76
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 35
- 241000282414 Homo sapiens Species 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 108020004707 nucleic acids Proteins 0.000 claims description 13
- 102000039446 nucleic acids Human genes 0.000 claims description 13
- 150000007523 nucleic acids Chemical class 0.000 claims description 13
- 208000030533 eye disease Diseases 0.000 claims description 9
- 208000034038 Pathologic Neovascularization Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 abstract description 23
- 235000018102 proteins Nutrition 0.000 description 69
- 108090000765 processed proteins & peptides Proteins 0.000 description 58
- 102000004196 processed proteins & peptides Human genes 0.000 description 57
- 229920001184 polypeptide Polymers 0.000 description 56
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 43
- 230000003993 interaction Effects 0.000 description 35
- 235000001014 amino acid Nutrition 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 30
- 150000001413 amino acids Chemical class 0.000 description 29
- 210000001508 eye Anatomy 0.000 description 29
- 206010028980 Neoplasm Diseases 0.000 description 28
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 23
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 238000002347 injection Methods 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 15
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 15
- 102000001708 Protein Isoforms Human genes 0.000 description 14
- 108010029485 Protein Isoforms Proteins 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 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 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 229920001223 polyethylene glycol Polymers 0.000 description 12
- 108020001580 protein domains Proteins 0.000 description 12
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 12
- 229940120638 avastin Drugs 0.000 description 11
- 201000011510 cancer Diseases 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 206010061218 Inflammation Diseases 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 229940076783 lucentis Drugs 0.000 description 9
- 241000588724 Escherichia coli Species 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 108091035707 Consensus sequence Proteins 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 102100035194 Placenta growth factor Human genes 0.000 description 7
- 230000033115 angiogenesis Effects 0.000 description 7
- 238000004925 denaturation Methods 0.000 description 7
- 230000036425 denaturation Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 230000002792 vascular Effects 0.000 description 7
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 206010038923 Retinopathy Diseases 0.000 description 6
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 6
- 230000001772 anti-angiogenic effect Effects 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- 201000011190 diabetic macular edema Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000001023 pro-angiogenic effect Effects 0.000 description 6
- 210000001525 retina Anatomy 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 5
- 208000017442 Retinal disease Diseases 0.000 description 5
- 239000000287 crude extract Substances 0.000 description 5
- 208000027866 inflammatory disease Diseases 0.000 description 5
- 208000002780 macular degeneration Diseases 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- 206010055113 Breast cancer metastatic Diseases 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 206010064930 age-related macular degeneration Diseases 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229940050526 hydroxyethylstarch Drugs 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 230000001394 metastastic effect Effects 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 108010087904 neutravidin Proteins 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 208000002815 pulmonary hypertension Diseases 0.000 description 4
- 238000002702 ribosome display Methods 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 201000004569 Blindness Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 101100263580 Canis lupus familiaris VEGFA gene Proteins 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 3
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 102000002111 Neuropilin Human genes 0.000 description 3
- 108050009450 Neuropilin Proteins 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 3
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 3
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000007792 addition Methods 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
- 239000004037 angiogenesis inhibitor Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000006320 pegylation Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000003606 umbilical vein Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 2
- 102000016904 Armadillo Domain Proteins Human genes 0.000 description 2
- 108010014223 Armadillo Domain Proteins Proteins 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 241000289632 Dasypodidae Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 206010024769 Local reaction Diseases 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108010082093 Placenta Growth Factor Proteins 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 2
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 2
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 2
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000035508 accumulation Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 108010081667 aflibercept Proteins 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000002983 circular dichroism Methods 0.000 description 2
- 238000000978 circular dichroism spectroscopy Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000003827 glycol group Chemical group 0.000 description 2
- 102000058223 human VEGFA Human genes 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229940092110 macugen Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 238000002428 photodynamic therapy Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 238000011555 rabbit model Methods 0.000 description 2
- 229960003876 ranibizumab Drugs 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 210000003705 ribosome Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- 238000002424 x-ray crystallography Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 108010005094 Advanced Glycation End Products Proteins 0.000 description 1
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
- 206010060934 Allergic oedema Diseases 0.000 description 1
- 208000000058 Anaplasia Diseases 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 102000009075 Angiopoietin-2 Human genes 0.000 description 1
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- 206010007687 Carotid artery stenosis Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 201000005262 Chondroma Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 239000012624 DNA alkylating agent Substances 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
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 1
- 102000002090 Fibronectin type III Human genes 0.000 description 1
- 108050009401 Fibronectin type III Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000009774 Follicular Cyst Diseases 0.000 description 1
- 206010018001 Gastrointestinal perforation Diseases 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000002125 Hemangioendothelioma Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 1
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 206010062904 Hormone-refractory prostate cancer Diseases 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 206010022773 Intracranial pressure increased Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- 206010024229 Leprosy Diseases 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 108050006654 Lipocalin Proteins 0.000 description 1
- 102000019298 Lipocalin Human genes 0.000 description 1
- 206010024612 Lipoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 206010025538 Malignant ascites Diseases 0.000 description 1
- 206010050513 Metastatic renal cell carcinoma Diseases 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 101100297639 Mus musculus Pigf gene Proteins 0.000 description 1
- 208000000592 Nasal Polyps Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 208000008558 Osteophyte Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001111421 Pannus Species 0.000 description 1
- 206010034665 Peritoneal fibrosis Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 101000766245 Pieris brassicae Bilin-binding protein Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 101900161471 Pseudomonas aeruginosa Exotoxin A Proteins 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 206010037649 Pyogenic granuloma Diseases 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 206010038935 Retinopathy sickle cell Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108050003978 Semaphorin Proteins 0.000 description 1
- 102000014105 Semaphorin Human genes 0.000 description 1
- 102000013008 Semaphorin-3A Human genes 0.000 description 1
- 108010090319 Semaphorin-3A Proteins 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 101000582398 Staphylococcus aureus Replication initiation protein Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 208000034698 Vitreous haemorrhage Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000012084 abdominal surgery Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960002833 aflibercept Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 230000027746 artery morphogenesis Effects 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 208000006170 carotid stenosis Diseases 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 201000005667 central retinal vein occlusion Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 210000004087 cornea Anatomy 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
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000037416 cystogenesis 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
- 108700041286 delta Proteins 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- VIYFPAMJCJLZKD-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate Chemical compound [Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 VIYFPAMJCJLZKD-UHFFFAOYSA-L 0.000 description 1
- NJDNXYGOVLYJHP-UHFFFAOYSA-L disodium;2-(3-oxido-6-oxoxanthen-9-yl)benzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=CC(=O)C=C2OC2=CC([O-])=CC=C21 NJDNXYGOVLYJHP-UHFFFAOYSA-L 0.000 description 1
- 101150109170 dll4 gene Proteins 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000008717 functional decline Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000002334 glycols Chemical group 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 201000009941 intracranial hypertension Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- 238000012804 iterative process Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000004901 leucine-rich repeat Anatomy 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000035168 lymphangiogenesis Effects 0.000 description 1
- 210000001077 lymphatic endothelium Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000027758 ovulation cycle Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000008756 pathogenetic mechanism Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 238000011197 physicochemical method Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 201000008312 primary pulmonary hypertension Diseases 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- 238000003157 protein complementation Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000006711 vascular endothelial growth factor production Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/515—Angiogenesic factors; Angiogenin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Ophthalmology & Optometry (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Vascular Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08168166 | 2008-11-03 | ||
| PCT/EP2009/064483 WO2010060748A1 (en) | 2008-11-03 | 2009-11-03 | Binding proteins inhibiting the vegf-a receptor interaction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2836948T3 true ES2836948T3 (es) | 2021-06-28 |
Family
ID=40149742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09756279T Active ES2836948T3 (es) | 2008-11-03 | 2009-11-03 | Proteínas de unión que inhiben la interacción del receptor de VEGF-A |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US8901076B2 (https=) |
| EP (2) | EP3785735A1 (https=) |
| JP (2) | JP5954990B2 (https=) |
| KR (1) | KR101698362B1 (https=) |
| CN (2) | CN107011425B (https=) |
| AU (1) | AU2009319204B2 (https=) |
| BR (1) | BRPI0921469B1 (https=) |
| CA (1) | CA2742241C (https=) |
| DK (1) | DK2358746T3 (https=) |
| ES (1) | ES2836948T3 (https=) |
| IL (1) | IL212589A (https=) |
| MX (2) | MX2011004649A (https=) |
| NZ (1) | NZ592591A (https=) |
| RU (2) | RU2550258C2 (https=) |
| WO (1) | WO2010060748A1 (https=) |
Families Citing this family (115)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9829494B2 (en) | 2005-12-01 | 2017-11-28 | Adrenomed Ag | Methods of treatment using ADM antibodies |
| RU2494108C2 (ru) | 2006-04-07 | 2013-09-27 | Аерпио Терапетикс, Инк. | Антитела, которые связывают человеческий белок бета-тирозин фосфатазу (нртрвета), и их использование |
| AU2014243418B2 (en) * | 2010-04-30 | 2016-09-22 | Molecular Partners Ag | Modified binding proteins inhibiting the VEGF-A receptor interaction |
| AR081361A1 (es) | 2010-04-30 | 2012-08-29 | Molecular Partners Ag | Proteinas de union modificadas que inhiben la interaccion de receptor del factor de crecimiento endotelial vascular de glicoproteina a vegf-a |
| PL2643349T3 (pl) * | 2010-11-26 | 2020-03-31 | Molecular Partners Ag | Zaprojektowane białka z powtórzeniami wiążące się z albuminą surowicy |
| EA201391607A1 (ru) | 2011-04-29 | 2014-04-30 | Янссен Байотек, Инк. | Связывающие il4/il13 белки с повторами и их применение |
| WO2012172054A1 (en) | 2011-06-16 | 2012-12-20 | Scil Proteins Gmbh | Modified multimeric ubiquitin proteins binding vegf-a |
| WO2013056240A1 (en) | 2011-10-13 | 2013-04-18 | Aerpio Therapeutics, Inc. | Methods for treating vascular leak syndrome and cancer |
| IL283215B2 (en) | 2011-11-16 | 2024-05-01 | Adrenomed Ag | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment and pharmaceutical compostions comprising the same |
| ES2494190T3 (es) | 2011-11-16 | 2014-09-15 | Adrenomed Ag | Anticuerpo anti-adrenomedulina (ADM) o fragmento de anticuerpo anti-ADM o andamiaje proteico sin Ig anti-ADM para reducir el riesgo de mortalidad en un paciente que padece una enfermedad crónica o aguda o un estado agudo |
| HRP20170427T1 (hr) | 2011-11-16 | 2017-06-16 | Sphingotec Gmbh | Testovi na adrenomedulin i postupci određivanja zrelog adrenomedulina |
| EP2780370B1 (en) | 2011-11-16 | 2019-09-25 | AdrenoMed AG | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for use in therapy of an acute disease or acute condition of a patient for stabilizing the circulation |
| LT3553084T (lt) | 2011-11-16 | 2023-03-10 | Adrenomed Ag | Anti-adrenomedulino (adm) antikūnas arba anti-adm antikūno fragmentas, arba anti-adm ne-ig karkasas, skirtas organų funkcijos sutrikimo arba organų nepakankamumo profilaktikai arba sumažinimui paciento, sergančio lėtine arba ūmine liga arba esančio ūminės būklės, organizme |
| PT2780371T (pt) | 2011-11-16 | 2019-01-30 | Adrenomed Ag | Anticorpo anti-adrenomedulina (adm) ou fragmento de anticorpo anti-adm ou uma estrutura não ig anti-adm para a regulação do equilíbrio de fluidos num doente com uma doença aguda ou crónica |
| CN103308673B (zh) | 2012-03-08 | 2017-05-31 | 思芬构技术有限公司 | 用于预测雌性对象中发生心血管事件的风险的方法 |
| CN103308670B (zh) | 2012-03-08 | 2017-06-09 | 思芬构技术有限公司 | 用于预测对象患糖尿病和/或代谢综合征的风险的方法 |
| CN103308689B (zh) | 2012-03-08 | 2017-04-12 | 思芬构技术有限公司 | 用于预测雌性对象中患上癌症的风险或诊断癌症的方法 |
| ES2753135T3 (es) * | 2012-05-07 | 2020-04-07 | Allergan Inc | Método de tratamiento de DMAE en pacientes resistentes a terapia anti-VEGF |
| PL3777834T3 (pl) | 2012-06-01 | 2022-05-30 | Novartis Ag | Strzykawka |
| WO2014001442A1 (en) * | 2012-06-28 | 2014-01-03 | Molecular Partners Ag | Designed ankyrin repeat proteins binding to platelet-derived growth factor |
| AU2012101677B4 (en) | 2012-07-03 | 2012-12-20 | Novartis Ag | Device |
| AU2013100070B4 (en) * | 2012-07-03 | 2013-04-04 | Novartis Ag | Use of device |
| DE202013000688U1 (de) | 2012-07-03 | 2013-03-05 | Novartis Ag | Glas-Spritze |
| EP2890389A1 (en) * | 2012-08-28 | 2015-07-08 | Novartis AG | Use of a vegf antagonist in treating ocular vascular proliferative diseases |
| US9664695B2 (en) | 2012-10-02 | 2017-05-30 | Sphingotec Gmbh | Method for diagnosing or monitoring kidney function or diagnosing kidney dysfunction |
| EP2738180A1 (en) | 2012-11-30 | 2014-06-04 | Molecular Partners AG | Binding proteins comprising at least two binding domains against HER2. |
| ES2879023T3 (es) | 2013-01-08 | 2021-11-19 | Sphingotec Gmbh | Niveles en ayunas de la hormona de crecimiento como marcador predictivo de riesgo cardiovascular |
| EP2961773B1 (en) * | 2013-02-26 | 2019-03-20 | Roche Glycart AG | Bispecific t cell activating antigen binding molecules |
| JP6649246B2 (ja) * | 2013-03-14 | 2020-02-19 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | タンパク質の徐放性送達の組成物及び製造プロセス中のタンパク質の安定化方法 |
| SG11201507774YA (en) | 2013-03-20 | 2015-10-29 | Sphingotec Gmbh | Adrenomedullin to guide therapy of blood pressure decline |
| FR3004650B1 (fr) * | 2013-04-22 | 2015-05-29 | Affilogic | Composition topique comprenant un variant d'une protéine sauvage à pli-OB, ainsi que son procédé de préparation |
| CN105209483B (zh) | 2013-05-31 | 2021-07-27 | 分子组合公司 | 与肝细胞生长因子结合的设计锚蛋白重复蛋白 |
| EP3010526A1 (en) | 2013-06-20 | 2016-04-27 | Novartis AG | Use of a vegf antagonist in treating macular edema |
| US20160137717A1 (en) | 2013-06-20 | 2016-05-19 | Gabriela Burian | Use of a vegf antagonist in treating choroidal neovascularisation |
| WO2014203181A1 (en) | 2013-06-20 | 2014-12-24 | Novartis Ag | Treatment of polypoidal choroidal vasculopathy |
| EP3019526A1 (en) | 2013-07-11 | 2016-05-18 | Novartis AG | Use of a vegf antagonist in treating chorioretinal neovascular and permeability disorders in paediatric patients |
| RU2676303C2 (ru) | 2013-07-11 | 2018-12-27 | Новартис Аг | Использование антагониста vegf для лечения ретролентальной фиброплазии |
| DK4374873T3 (da) | 2013-07-12 | 2025-11-03 | Astellas Us Llc | Middel til brug ved behandling eller forebyggelse af oftalmologiske tilstande |
| PT3065761T (pt) * | 2013-11-05 | 2020-02-21 | Allergan Inc | Método de tratamento de condições oculares com um darpin anti-vegf |
| CN106456757A (zh) | 2014-05-12 | 2017-02-22 | 福尔密孔股份公司 | 含有vegf拮抗剂的预填充塑料注射器 |
| EP3002589A1 (en) | 2014-10-01 | 2016-04-06 | sphingotec GmbH | A method for stratifying a female subject for hormone replacement therapy |
| KR102427117B1 (ko) * | 2015-04-02 | 2022-07-29 | 몰리큘라 파트너스 아게 | 혈청 알부민에 대한 결합 특이성을 갖는 설계된 안키린 반복 도메인 |
| CN107667294B (zh) | 2015-04-24 | 2021-12-17 | 思芬构技术有限公司 | 用于预测慢性肾病发生风险的方法 |
| TWI799366B (zh) | 2015-09-15 | 2023-04-21 | 美商建南德克公司 | 胱胺酸結骨架平臺 |
| CA3005132A1 (en) | 2015-11-18 | 2017-05-26 | Sio2 Medical Products, Inc. | Coated syringe for ophthalmic formulations containing a vegf antagonist |
| EP3377100B1 (en) | 2015-11-18 | 2025-02-26 | Formycon AG | Pre-filled pharmaceutical package comprising a liquid formulation of a vegf-antagonist |
| CN108290004A (zh) | 2015-11-18 | 2018-07-17 | 福尔密孔股份公司 | 含有vegf拮抗剂的预填充塑料注射器 |
| WO2018218013A2 (en) | 2017-05-24 | 2018-11-29 | Sio2 Medical Products, Inc. | Sterilizable pharmaceutical package for ophthalmic formulations |
| US10576128B2 (en) | 2016-01-26 | 2020-03-03 | Formycon Ag | Liquid formulation of a VEGF antagonist |
| CN115951066A (zh) | 2016-02-29 | 2023-04-11 | 麦恩泰科特有限公司 | 可用于治疗湿性年龄相关性黄斑变性的预测性标志物 |
| DE112017002105T5 (de) | 2016-04-21 | 2019-04-25 | Sphingotec Therapeutics Gmbh | Verfahren zur Bestimmung von DPP3 und therapeutische Verfahren |
| EP3474887A1 (en) | 2016-06-27 | 2019-05-01 | AiCuris Anti-infective Cures GmbH | Hcmv entry inhibitors |
| RU2019103403A (ru) | 2016-07-08 | 2020-08-10 | Сфинготек Гмбх | Адреномедуллин для оценки застоя у индивидуума с острой сердечной недостаточностью |
| BR112019001206A2 (pt) | 2016-07-20 | 2019-06-25 | Aerpio Therapeutics Inc | anticorpos monoclonais humanizados que visam ve-ptp (hptp-ss) |
| CN109790206A (zh) | 2016-09-22 | 2019-05-21 | 分子组合公司 | 重组结合蛋白及其用途 |
| EP3309550A1 (en) | 2016-10-12 | 2018-04-18 | sphingotec GmbH | Method for the detection of apolipoprotein e4 |
| EP3339324A1 (en) | 2016-12-22 | 2018-06-27 | sphingotec GmbH | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for use in intervention and therapy of congestion in a patient in need thereof |
| JP7727371B2 (ja) | 2016-12-16 | 2025-08-21 | アドレノメト アクチェンゲゼルシャフト | うっ血の処置と治療を必要とする患者でその処置と治療に使用するための抗アドレノメデュリン（ＡＤＭ）抗体、または抗ＡＤＭ抗体フラグメント、または抗ＡＤＭ非Ｉｇ足場 |
| WO2018215580A1 (en) | 2017-05-24 | 2018-11-29 | Formycon Ag | Method for sterilizing prefilled plastic syringes containing a vegf antagonist |
| EP3630043A1 (en) | 2017-05-24 | 2020-04-08 | Formycon AG | Sterilizable pre-filled pharmaceutical packages comprising a liquid formulation of a vegf-antagonist |
| EP3631459A1 (en) | 2017-05-30 | 2020-04-08 | SphingoTec GmbH | A method for diagnosing or monitoring kidney function or diagnosing kidney dysfunction |
| 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 |
| KR20200038303A (ko) * | 2017-08-18 | 2020-04-10 | 캠브리지 엔터프라이즈 리미티드 | 모듈형 결합 단백질 |
| HRP20241795T1 (hr) | 2017-09-25 | 2025-03-14 | Adrenomed Ag | Anti-adrenomedulin (adm) – vezujući entitet za uporabu u terapiji ili prevenciji simptoma bolesti |
| WO2019077082A1 (en) | 2017-10-18 | 2019-04-25 | Adrenomed Ag | SURVEILLANCE OF THERAPY UNDER TREATMENT WITH ANTI-ADRENOMEDULIN BINDER (ADM) |
| JP7411546B2 (ja) | 2017-10-24 | 2024-01-11 | シュピーンゴテック ゲゼルシャフト ミット ベシュレンクテル ハフツング | 初回心血管イベントの予測のためのセレノプロテインｐ |
| KR102835427B1 (ko) | 2017-10-25 | 2025-07-21 | 4틴4 파마슈티컬스 게엠베하 | 특이적 dpp3-에피토프에 대하여 지시되고 이에 결합하는 dpp3 결합제 및 산화적 스트레스와 연관되는 질환 / 급성 병태의 예방 또는 치료에서의 그의 용도 |
| CN119770645A (zh) | 2018-02-08 | 2025-04-08 | 斯弗因高泰克有限公司 | 用于诊断和/或预测痴呆症的肾上腺髓质素和抗肾上腺髓质素结合物在治疗或预防痴呆症中的应用 |
| EP3569614A1 (en) | 2018-05-18 | 2019-11-20 | Julius-Maximilians-Universität Würzburg | Compounds and methods for the immobilization of myostatin-inhibitors on the extracellular matrix by transglutaminase |
| EP3586865A1 (en) | 2018-06-21 | 2020-01-01 | Charité - Universitätsmedizin Berlin | Complement anaphylatoxin binders and their use in treatment of a subject having an ocular wound and/or fibrosis |
| WO2020068653A1 (en) | 2018-09-24 | 2020-04-02 | Aerpio Pharmaceuticals, Inc. | MULTISPECIFIC ANTIBODIES THAT TARGET HPTP - β (VE-PTP) AND VEGF |
| BR112021010069A2 (pt) | 2018-12-20 | 2021-11-23 | Sphingotec Gmbh | Selenoproteína p em insuficiência cardíaca |
| CN113557031A (zh) | 2018-12-21 | 2021-10-26 | 4Teen4制药有限公司 | 使用血管紧张肽受体激动剂和/或其前体的治疗的疗法指导和/或疗法监测 |
| WO2020245746A1 (en) | 2019-06-04 | 2020-12-10 | Molecular Partners Ag | Multispecific proteins |
| AU2020328194A1 (en) | 2019-08-15 | 2022-03-17 | Sphingotec Gmbh | A method for diagnosing or monitoring kidney function or diagnosing kidney dysfunction in pediatric patients |
| JP2022546061A (ja) | 2019-08-30 | 2022-11-02 | ４ティーン４ ファーマシューティカルズ ゲゼルシャフト ミット ベシュレンクテル ハフツング | ショック症治療のための治療法の誘導および／または治療法の監視 |
| IL293698A (en) | 2019-12-11 | 2022-08-01 | Molecular Partners Ag | Recombinant peptide-mhc complex binding proteins, their production and use |
| EP3871689A1 (en) | 2020-02-26 | 2021-09-01 | sphingotec GmbH | Anti-adm-antibodies binding to the free n-terminus for accelerated transition of adm-gly to bio-adm in patients with adm-gly/ bio-adm ratio above a threshold and combination with vitamin c |
| CN115244080A (zh) | 2020-02-27 | 2022-10-25 | 艾德里诺医药公司 | 用于治疗或预防休克的抗肾上腺髓质素(ADM)抗体或抗ADM抗体片段或抗ADM非Ig支架 |
| US20230193348A1 (en) | 2020-02-27 | 2023-06-22 | 4TEEN4 Pharmaceuticals GmbH | Dpp3 for therapy guidance, monitoring and stratification of nt-adm antibodies in patients with shock |
| US20230250166A1 (en) | 2020-02-27 | 2023-08-10 | Adrenomed Ag | Anti-adrenomedullin (adm) binder for use in therapy of patients in shock |
| EP3922993A1 (en) | 2020-06-12 | 2021-12-15 | 4TEEN4 Pharmaceuticals GmbH | Dpp3 in patients infected with coronavirus |
| AU2021238591A1 (en) | 2020-03-16 | 2022-11-17 | Adrenomed Ag | Pro-Adrenomedullin or fragment thereof in patients infected with Corona virus and treatments with binder against adrenomedullin |
| BR112022017277A2 (pt) | 2020-03-16 | 2022-10-18 | 4TEEN4 Pharmaceuticals GmbH | Dpp3 em pacientes infectados com coronavírus |
| JP2023525518A (ja) | 2020-05-06 | 2023-06-16 | モレキュラー パートナーズ アクチェンゲゼルシャフト | 新規アンキリンリピート結合タンパク質とその用途 |
| US20240279290A1 (en) | 2020-05-14 | 2024-08-22 | Molecular Partners Ag | Multispecific proteins |
| EP4023218A1 (en) | 2020-12-02 | 2022-07-06 | S-Form Pharma | Combination therapy for patients having acute and/or persistent dyspnea |
| AU2021403833A1 (en) | 2020-12-16 | 2023-07-27 | Molecular Partners Ag | Novel slow-release prodrugs |
| CA3211368A1 (en) | 2021-03-09 | 2022-09-15 | Molecular Partners Ag | Novel darpin based cd123 engagers |
| US20240317852A1 (en) | 2021-03-09 | 2024-09-26 | Molecular Partners Ag | Novel darpin based cd33 engagers |
| BR112023018293A2 (pt) | 2021-03-09 | 2023-10-31 | Molecular Partners Ag | Acopladores de célula t multiespecíficos à base de darpin |
| EP4305063A1 (en) | 2021-03-09 | 2024-01-17 | Molecular Partners AG | Protease cleavable prodrugs |
| BR112023022439A2 (pt) | 2021-04-26 | 2023-12-26 | Celanese Eva Performance Polymers Llc | Dispositivo implantável para liberação sustentada de um composto de fármaco macromolecular |
| CN117529664A (zh) | 2021-06-18 | 2024-02-06 | 思芬构技术有限公司 | 用于预测脓毒症和脓毒性休克的方法 |
| US20240310387A1 (en) | 2021-06-29 | 2024-09-19 | Berysol Gmbh | Composite biomarker for the identification of selenium deficiency in a bodily fluid |
| EP4145456A1 (en) | 2021-09-06 | 2023-03-08 | Bayer AG | Prediction of a change related to a macular fluid |
| WO2023110983A1 (en) | 2021-12-14 | 2023-06-22 | Molecular Partners Ag | Designed repeat domains with dual binding specificity and their use |
| CA3254142A1 (en) | 2022-03-15 | 2023-09-21 | Adrenomed Ag | STABLE AQUEOUS FORMULATION OF AN ANTI-ADRENOMEDULLIN (ADM) ANTIBODY OR AN ANTI-ADM ANTIBODY FRAGMENT |
| AU2023315168A1 (en) | 2022-07-29 | 2025-02-13 | 4TEEN4 Pharmaceuticals GmbH | Prediction of an increase of dpp3 in a patient with septic shock |
| AU2023313376A1 (en) | 2022-07-29 | 2025-03-06 | Adrenomed Ag | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for use in therapy or prevention of shock |
| WO2024028278A1 (en) | 2022-08-01 | 2024-02-08 | Molecular Partners Ag | Charge modified designed repeat domains and their use |
| WO2024038307A1 (en) | 2022-08-19 | 2024-02-22 | Novartis Ag | Dosing regimens for sars-cov-2 binding molecules |
| WO2024059686A2 (en) * | 2022-09-15 | 2024-03-21 | The Regents Of The University Of California | Darpin backbones and rigidified electron microscopy imaging scaffolds |
| JP2025541138A (ja) | 2022-12-15 | 2025-12-18 | ４ティーン４ ファーマシューティカルズ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 重篤な患者における肺機能の改善のためのｄｐｐ３阻害剤 |
| EP4673159A1 (en) | 2023-02-27 | 2026-01-07 | Molecular Partners AG | Darpins for use in reducing renal accumulation of drugs |
| JP2026510789A (ja) | 2023-03-17 | 2026-04-10 | ペーアーエム セラノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | ペプチジルグリシンα－アミド化モノオキシゲナーゼ（ＰＡＭ）の測定法及び診断目的のためのその使用 |
| EP4687942A1 (en) | 2023-03-29 | 2026-02-11 | 4TEEN4 Pharmaceuticals GmbH | Dpp3 inhibitor for myocardial protection and prevention of myocardial injury in critically ill patients with blood pressure decline |
| CN121889677A (zh) | 2023-09-25 | 2026-04-17 | 思芬构技术有限公司 | 用于肾移植患者中移植物功能降低的早期诊断、早期预测、监测或严重程度预测的方法 |
| WO2025146491A1 (en) | 2024-01-05 | 2025-07-10 | Molecular Partners Ag | Designed repeat domains with dual binding specificity for cd117 and cd47-binding agent |
| WO2025229075A1 (en) | 2024-05-03 | 2025-11-06 | Sphingotec Gmbh | A method for the specific determination of proenkephalin fragment 119-159 |
| WO2025248139A1 (en) | 2024-05-31 | 2025-12-04 | 4TEEN4 Pharmaceuticals GmbH | Use of adrenomedullin or fragments thereof in the treatment of a patient in need thereof |
| EP4675277A1 (en) | 2024-07-05 | 2026-01-07 | Predemtec AG | A method for diagnosing alzheimer´s disease or determining the risk of suffering from alzheimer´s disease |
| WO2026046968A1 (en) | 2024-08-26 | 2026-03-05 | 4TEEN4 Pharmaceuticals GmbH | Dpp3 binders for the treatment of endothelial dysfunction |
| WO2026046978A1 (en) | 2024-08-26 | 2026-03-05 | Pam Theragnostics Gmbh | Anti-adm antibodies, anti-adm antibody fragment or anti-adm non-ig scaffold for therapy or prevention of immune effector cell therapy side effects |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0436597B1 (en) | 1988-09-02 | 1997-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| US5348867A (en) | 1991-11-15 | 1994-09-20 | George Georgiou | Expression of proteins on bacterial surface |
| IL117645A (en) | 1995-03-30 | 2005-08-31 | Genentech Inc | Vascular endothelial cell growth factor antagonists for use as medicaments in the treatment of age-related macular degeneration |
| CA2196496A1 (en) | 1997-01-31 | 1998-07-31 | Stephen William Watson Michnick | Protein fragment complementation assay for the detection of protein-protein interactions |
| PT971959E (pt) | 1997-04-07 | 2006-05-31 | Genentech Inc | Anticorpos humanizados e metodos para formar anticorpos humanizados |
| KR100816621B1 (ko) | 1997-04-07 | 2008-03-24 | 제넨테크, 인크. | 항-ｖｅｇｆ 항체 |
| EP0975748B1 (en) | 1997-04-23 | 2006-03-29 | Universität Zürich | Methods for identifying nucleic acid molecules encoding (poly)peptides that interact with target molecules |
| NZ511699A (en) | 1998-12-02 | 2003-02-28 | Phylos Inc | DNA-protein fusions and uses thereof |
| US7087411B2 (en) * | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| CN101433715B (zh) | 1999-06-08 | 2013-04-17 | 里珍纳龙药品有限公司 | 具有改善的药物动力学特性的修饰嵌合多肽 |
| EP1332209B1 (en) * | 2000-09-08 | 2009-11-11 | Universität Zürich | Collections of repeat proteins comprising repeat modules |
| RU2299208C2 (ru) * | 2001-05-08 | 2007-05-20 | Шеринг Акциенгезельшафт | Антраниламидпиридинамиды избирательного действия в качестве ингибиторов vegfr-2 и vegfr-3 |
| US7696320B2 (en) | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| US7772188B2 (en) * | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1711196A4 (en) * | 2003-12-05 | 2011-09-14 | Bristol Myers Squibb Co | INHIBITORS OF TYPE-2 VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTORS |
| JP2008519590A (ja) * | 2004-11-12 | 2008-06-12 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | 組換えニューカッスル病ウィルス |
| ES2633574T3 (es) * | 2005-03-25 | 2017-09-22 | Regeneron Pharmaceuticals, Inc. | Formulaciones de antagonistas de VEGF |
| BRPI0613593A2 (pt) | 2005-07-08 | 2011-01-18 | Univ Zuerich | método de teste "phage display" filamentoso, vetor de fago ou de fagomìdeo e biblioteca de vetores de fago ou fagomìdeo |
| MX2009005466A (es) | 2006-11-22 | 2009-08-17 | Adnexus A Bristol Myers Sqibb | Terapeuticos dirigidos a base de proteinas manipuladas para receptores de tirosina cinasas, incluyendo receptor de factor de crecimiento tipo insulina-i. |
| BRPI0806414A2 (pt) * | 2007-02-01 | 2011-09-06 | Genentech Inc | método para tratamento de tumor |
| EP2111228B1 (en) | 2007-02-02 | 2011-07-20 | Bristol-Myers Squibb Company | 10Fn3 domain for use in treating diseases associated with inappropriate angiogenesis |
-
2009
- 2009-11-03 BR BRPI0921469-0A patent/BRPI0921469B1/pt active IP Right Grant
- 2009-11-03 RU RU2011122201/10A patent/RU2550258C2/ru active
- 2009-11-03 MX MX2011004649A patent/MX2011004649A/es unknown
- 2009-11-03 MX MX2015010520A patent/MX359570B/es unknown
- 2009-11-03 ES ES09756279T patent/ES2836948T3/es active Active
- 2009-11-03 US US13/126,821 patent/US8901076B2/en active Active
- 2009-11-03 AU AU2009319204A patent/AU2009319204B2/en active Active
- 2009-11-03 DK DK09756279.7T patent/DK2358746T3/da active
- 2009-11-03 RU RU2015108838A patent/RU2650765C1/ru active
- 2009-11-03 JP JP2011533752A patent/JP5954990B2/ja active Active
- 2009-11-03 CA CA2742241A patent/CA2742241C/en active Active
- 2009-11-03 EP EP20196328.7A patent/EP3785735A1/en not_active Withdrawn
- 2009-11-03 KR KR1020117009012A patent/KR101698362B1/ko active Active
- 2009-11-03 EP EP09756279.7A patent/EP2358746B1/en active Active
- 2009-11-03 CN CN201710092752.9A patent/CN107011425B/zh active Active
- 2009-11-03 WO PCT/EP2009/064483 patent/WO2010060748A1/en not_active Ceased
- 2009-11-03 CN CN2009801536047A patent/CN102272148A/zh active Pending
- 2009-11-03 NZ NZ592591A patent/NZ592591A/en unknown
-
2011
- 2011-04-28 IL IL212589A patent/IL212589A/en active IP Right Grant
-
2014
- 2014-10-28 US US14/525,553 patent/US20150344539A1/en not_active Abandoned
-
2015
- 2015-03-17 JP JP2015053249A patent/JP6329503B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| DK2358746T3 (da) | 2020-12-21 |
| CA2742241A1 (en) | 2010-06-03 |
| CN107011425B (zh) | 2021-01-01 |
| MX359570B (es) | 2018-10-01 |
| JP5954990B2 (ja) | 2016-07-20 |
| JP2015133978A (ja) | 2015-07-27 |
| CN102272148A (zh) | 2011-12-07 |
| JP2012507271A (ja) | 2012-03-29 |
| RU2650765C1 (ru) | 2018-04-17 |
| AU2009319204A1 (en) | 2010-06-03 |
| AU2009319204B2 (en) | 2014-11-13 |
| KR101698362B1 (ko) | 2017-01-20 |
| KR20110082528A (ko) | 2011-07-19 |
| RU2011122201A (ru) | 2012-12-10 |
| WO2010060748A1 (en) | 2010-06-03 |
| BRPI0921469A2 (pt) | 2016-01-12 |
| EP2358746B1 (en) | 2020-09-16 |
| US20150344539A1 (en) | 2015-12-03 |
| CN107011425A (zh) | 2017-08-04 |
| EP3785735A1 (en) | 2021-03-03 |
| EP2358746A1 (en) | 2011-08-24 |
| IL212589A (en) | 2017-01-31 |
| RU2550258C2 (ru) | 2015-05-10 |
| NZ592591A (en) | 2012-04-27 |
| IL212589A0 (en) | 2011-07-31 |
| MX2011004649A (es) | 2011-05-30 |
| US8901076B2 (en) | 2014-12-02 |
| CA2742241C (en) | 2019-12-10 |
| BRPI0921469B1 (pt) | 2022-01-18 |
| US20110207668A1 (en) | 2011-08-25 |
| JP6329503B2 (ja) | 2018-05-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2836948T3 (es) | Proteínas de unión que inhiben la interacción del receptor de VEGF-A | |
| ES2745491T3 (es) | Proteínas de unión modificadas que inhiben la interacción del receptor VEGF-A | |
| HK1238258B (zh) | 抑制vegf-a受体相互作用的结合蛋白 | |
| HK1179876B (en) | Modified binding proteins inhibiting the vegf-a receptor interaction | |
| AU2014243418A1 (en) | Modified binding proteins inhibiting the VEGF-A receptor interaction | |
| HK1179876A (en) | Modified binding proteins inhibiting the vegf-a receptor interaction |