CA2858962C - Compositions of human tear lipocalin muteins and methods of use thereof - Google Patents
Compositions of human tear lipocalin muteins and methods of use thereof Download PDFInfo
- Publication number
- CA2858962C CA2858962C CA2858962A CA2858962A CA2858962C CA 2858962 C CA2858962 C CA 2858962C CA 2858962 A CA2858962 A CA 2858962A CA 2858962 A CA2858962 A CA 2858962A CA 2858962 C CA2858962 C CA 2858962C
- Authority
- CA
- Canada
- Prior art keywords
- amino acid
- fragment
- lipocalin mutein
- acid position
- lipocalin
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 69
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title abstract description 30
- 102000003816 Interleukin-13 Human genes 0.000 claims abstract description 90
- 108090000176 Interleukin-13 Proteins 0.000 claims abstract description 90
- 108090000978 Interleukin-4 Proteins 0.000 claims abstract description 81
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 76
- 208000035475 disorder Diseases 0.000 claims abstract description 50
- 210000004072 lung Anatomy 0.000 claims abstract description 42
- 208000006673 asthma Diseases 0.000 claims abstract description 31
- 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 15
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 10
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims abstract description 10
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims abstract description 10
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims abstract description 10
- 201000009961 allergic asthma Diseases 0.000 claims abstract description 10
- 208000005069 pulmonary fibrosis Diseases 0.000 claims abstract description 9
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 8
- 206010001881 Alveolar proteinosis Diseases 0.000 claims abstract description 6
- 201000003489 pulmonary alveolar proteinosis Diseases 0.000 claims abstract description 6
- 206010039083 rhinitis Diseases 0.000 claims abstract description 6
- 102000019298 Lipocalin Human genes 0.000 claims description 202
- 108050006654 Lipocalin Proteins 0.000 claims description 202
- 102000004388 Interleukin-4 Human genes 0.000 claims description 81
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 75
- 239000012634 fragment Substances 0.000 claims description 65
- 102000005962 receptors Human genes 0.000 claims description 37
- 108020003175 receptors Proteins 0.000 claims description 37
- 102100039078 Interleukin-4 receptor subunit alpha Human genes 0.000 claims description 31
- 108010038486 Interleukin-4 Receptors Proteins 0.000 claims description 29
- 101710169536 Interleukin-4 receptor subunit alpha Proteins 0.000 claims description 29
- 102000010787 Interleukin-4 Receptors Human genes 0.000 claims description 28
- 201000010099 disease Diseases 0.000 claims description 26
- 108020001507 fusion proteins Proteins 0.000 claims description 25
- 102000037865 fusion proteins Human genes 0.000 claims description 25
- 101001076430 Homo sapiens Interleukin-13 Proteins 0.000 claims description 23
- 102000019207 human interleukin-13 Human genes 0.000 claims description 23
- 238000001727 in vivo Methods 0.000 claims description 19
- 230000001225 therapeutic effect Effects 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 17
- 101710139422 Eotaxin Proteins 0.000 claims description 16
- 102100023688 Eotaxin Human genes 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 16
- 210000002175 goblet cell Anatomy 0.000 claims description 15
- 230000002401 inhibitory effect Effects 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 14
- 206010054949 Metaplasia Diseases 0.000 claims description 13
- 230000015689 metaplastic ossification Effects 0.000 claims description 13
- 239000000443 aerosol Substances 0.000 claims description 12
- 230000008506 pathogenesis Effects 0.000 claims description 11
- 208000019693 Lung disease Diseases 0.000 claims description 10
- 230000028993 immune response Effects 0.000 claims description 10
- 230000037361 pathway Effects 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 8
- 230000004054 inflammatory process Effects 0.000 claims description 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 8
- 230000003266 anti-allergic effect Effects 0.000 claims description 7
- 229920001184 polypeptide Polymers 0.000 claims description 7
- 230000007783 downstream signaling Effects 0.000 claims description 6
- 230000003389 potentiating effect Effects 0.000 claims description 6
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 230000005714 functional activity Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 4
- 102000002090 Fibronectin type III Human genes 0.000 claims description 4
- 108050009401 Fibronectin type III Proteins 0.000 claims description 4
- 102000004557 Interleukin-18 Receptors Human genes 0.000 claims description 4
- 108010017537 Interleukin-18 Receptors Proteins 0.000 claims description 4
- 102100036672 Interleukin-23 receptor Human genes 0.000 claims description 4
- 101710195550 Interleukin-23 receptor Proteins 0.000 claims description 4
- 102000010781 Interleukin-6 Receptors Human genes 0.000 claims description 4
- 108010038501 Interleukin-6 Receptors Proteins 0.000 claims description 4
- 101001033311 Mus musculus Interleukin-4 receptor subunit alpha Proteins 0.000 claims description 4
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 4
- 230000036755 cellular response Effects 0.000 claims description 4
- 241001515942 marmosets Species 0.000 claims description 4
- 102000042286 type I cytokine receptor family Human genes 0.000 claims description 4
- 108091052247 type I cytokine receptor family Proteins 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 abstract description 46
- 102000004169 proteins and genes Human genes 0.000 abstract description 38
- 206010010741 Conjunctivitis Diseases 0.000 abstract description 5
- 230000029069 type 2 immune response Effects 0.000 abstract description 5
- 235000018102 proteins Nutrition 0.000 description 37
- 239000005557 antagonist Substances 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 23
- 210000001519 tissue Anatomy 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 18
- 102000003752 Lipocalin 1 Human genes 0.000 description 17
- 108010057281 Lipocalin 1 Proteins 0.000 description 17
- 101001033312 Homo sapiens Interleukin-4 receptor subunit alpha Proteins 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 230000004044 response Effects 0.000 description 13
- 238000009472 formulation Methods 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 102000054663 human IL4R Human genes 0.000 description 11
- 230000001976 improved effect Effects 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 208000037883 airway inflammation Diseases 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 210000000981 epithelium Anatomy 0.000 description 9
- 239000006199 nebulizer Substances 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 150000007523 nucleic acids Chemical class 0.000 description 9
- 125000003729 nucleotide group Chemical group 0.000 description 9
- 206010016654 Fibrosis Diseases 0.000 description 8
- 108010089995 Interleukin-13 Receptor alpha1 Subunit Proteins 0.000 description 8
- 102000008035 Interleukin-13 Receptor alpha1 Subunit Human genes 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000004761 fibrosis Effects 0.000 description 8
- 210000003097 mucus Anatomy 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 230000009285 allergic inflammation Effects 0.000 description 7
- 230000001668 ameliorated effect Effects 0.000 description 7
- 230000002163 immunogen Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 206010020751 Hypersensitivity Diseases 0.000 description 6
- 229920001213 Polysorbate 20 Polymers 0.000 description 6
- 230000004888 barrier function Effects 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000003843 mucus production Effects 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 6
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 6
- 210000004988 splenocyte Anatomy 0.000 description 6
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 5
- 108010083698 Chemokine CCL26 Proteins 0.000 description 5
- 101001003135 Homo sapiens Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 5
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 5
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 5
- 102100035405 Neutrophil gelatinase-associated lipocalin Human genes 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 238000002663 nebulization Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000011830 transgenic mouse model Methods 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 102000004559 Interleukin-13 Receptors Human genes 0.000 description 4
- 108010017511 Interleukin-13 Receptors Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 208000030961 allergic reaction Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 102000055229 human IL4 Human genes 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 108040006852 interleukin-4 receptor activity proteins Proteins 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 101710189812 Bilin-binding protein Proteins 0.000 description 3
- 108010051335 Lipocalin-2 Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 102000013968 STAT6 Transcription Factor Human genes 0.000 description 3
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- -1 biliverdins Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 229940028885 interleukin-4 Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229940068977 polysorbate 20 Drugs 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006474 Bronchopulmonary aspergillosis allergic Diseases 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
- 206010012434 Dermatitis allergic Diseases 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102100034789 Epididymal-specific lipocalin-6 Human genes 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000945886 Homo sapiens Epididymal-specific lipocalin-6 Proteins 0.000 description 2
- 101001023833 Homo sapiens Neutrophil gelatinase-associated lipocalin Proteins 0.000 description 2
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 2
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 2
- 102000042838 JAK family Human genes 0.000 description 2
- 108091082332 JAK family Proteins 0.000 description 2
- 102100034724 Lipocalin-1 Human genes 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101100340762 Mus musculus Il4r gene Proteins 0.000 description 2
- 101710147507 Neutrophil gelatinase-associated lipocalin Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 102000015774 TYK2 Kinase Human genes 0.000 description 2
- 108010010057 TYK2 Kinase Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000009824 affinity maturation Effects 0.000 description 2
- 210000001552 airway epithelial cell Anatomy 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 2
- 208000002205 allergic conjunctivitis Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 208000024998 atopic conjunctivitis Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000004890 epithelial barrier function Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000012781 high pressure - size exclusion chromatography Methods 0.000 description 2
- 102000047202 human LCN2 Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000004727 humoral immunity Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 238000012261 overproduction Methods 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 102000029752 retinol binding Human genes 0.000 description 2
- 108091000053 retinol binding Proteins 0.000 description 2
- 201000000306 sarcoidosis Diseases 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000012906 subvisible particle Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000032258 transport Effects 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
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 101150084750 1 gene Proteins 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 108020004463 18S ribosomal RNA Proteins 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100022954 Apolipoprotein D Human genes 0.000 description 1
- 108010025614 Apolipoproteins D Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 102100039536 Calcium-activated chloride channel regulator 1 Human genes 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- 206010016946 Food allergy Diseases 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000888572 Homo sapiens Calcium-activated chloride channel regulator 1 Proteins 0.000 description 1
- 101000605055 Homo sapiens Epididymal-specific lipocalin-8 Proteins 0.000 description 1
- 101100232357 Homo sapiens IL13RA1 gene Proteins 0.000 description 1
- 101001095308 Homo sapiens Periostin Proteins 0.000 description 1
- 101000609261 Homo sapiens Plasminogen activator inhibitor 2 Proteins 0.000 description 1
- 101000835023 Homo sapiens Transcription factor A, mitochondrial Proteins 0.000 description 1
- 101000800287 Homo sapiens Tubulointerstitial nephritis antigen-like Proteins 0.000 description 1
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000007482 Interleukin-13 Receptor alpha2 Subunit Human genes 0.000 description 1
- 108010085418 Interleukin-13 Receptor alpha2 Subunit Proteins 0.000 description 1
- 101710112663 Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000000585 Interleukin-9 Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000000785 Invasive Pulmonary Aspergillosis Diseases 0.000 description 1
- 108010024121 Janus Kinases Proteins 0.000 description 1
- 102000015617 Janus Kinases Human genes 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-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
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-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
- 241001417534 Lutjanidae Species 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
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108090000143 Mouse Proteins Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000978390 Mus musculus Eotaxin Proteins 0.000 description 1
- 101100232358 Mus musculus Il13ra1 gene Proteins 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100032341 PCNA-interacting partner Human genes 0.000 description 1
- 101710196737 PCNA-interacting partner Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102100037765 Periostin Human genes 0.000 description 1
- 101710199268 Periostin Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 102100039419 Plasminogen activator inhibitor 2 Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102100026155 Transcription factor A, mitochondrial Human genes 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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100033469 Tubulointerstitial nephritis antigen-like Human genes 0.000 description 1
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 1
- 101710153009 Uterocalin Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 210000005091 airway smooth muscle Anatomy 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 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
- 230000004075 alteration Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 210000004082 barrier epithelial cell Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 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
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 238000013357 binding ELISA Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000003508 chemical denaturation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000011262 co‐therapy Methods 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 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
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 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
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 210000004090 human X chromosome Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000004047 hyperresponsiveness Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940125369 inhaled corticosteroids Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012538 light obscuration Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940125386 long-acting bronchodilator Drugs 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000014925 multi-organism signaling Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 108010067198 mutein 2 Proteins 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 229960000470 omalizumab Drugs 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000004923 pancreatic tissue Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000001322 periplasm 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
- 239000003016 pheromone Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000012383 pulmonary drug delivery Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 108700015048 receptor decoy activity proteins Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000008786 sensory perception of smell Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
- 108091005475 signaling receptors Proteins 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000009102 step therapy Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000012905 visible particle Substances 0.000 description 1
- 238000011179 visual inspection Methods 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
- 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Otolaryngology (AREA)
- Marine Sciences & Fisheries (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161570018P | 2011-12-13 | 2011-12-13 | |
| US61/570,018 | 2011-12-13 | ||
| PCT/EP2012/075146 WO2013087660A1 (en) | 2011-12-13 | 2012-12-12 | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2858962A1 CA2858962A1 (en) | 2013-06-20 |
| CA2858962C true CA2858962C (en) | 2023-09-05 |
Family
ID=47552959
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2858962A Active CA2858962C (en) | 2011-12-13 | 2012-12-12 | Compositions of human tear lipocalin muteins and methods of use thereof |
Country Status (13)
| Country | Link |
|---|---|
| US (6) | US9572863B2 (cg-RX-API-DMAC7.html) |
| EP (3) | EP2790719B1 (cg-RX-API-DMAC7.html) |
| JP (5) | JP6163162B2 (cg-RX-API-DMAC7.html) |
| CN (2) | CN109432402B (cg-RX-API-DMAC7.html) |
| AU (1) | AU2012350660B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2858962C (cg-RX-API-DMAC7.html) |
| DK (2) | DK3453400T3 (cg-RX-API-DMAC7.html) |
| ES (2) | ES2863410T3 (cg-RX-API-DMAC7.html) |
| HU (2) | HUE042720T2 (cg-RX-API-DMAC7.html) |
| PL (2) | PL3453400T3 (cg-RX-API-DMAC7.html) |
| SG (2) | SG10201604566QA (cg-RX-API-DMAC7.html) |
| TR (1) | TR201901826T4 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2013087660A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8986951B2 (en) * | 2010-06-08 | 2015-03-24 | Pieris Ag | Tear lipocalin in muteins binding IL-4 R alpha |
| TR201901826T4 (tr) * | 2011-12-13 | 2019-03-21 | Astrazeneca Ab | Il-4 ve/veya ıl-13'ün ilgili reseptörlerine bağlanmasını inhibe ederek belirli rahatsızlıkların önlenmesi ya da tedavi edilmesi için yöntemler. |
| SG10201912019WA (en) * | 2014-05-22 | 2020-02-27 | Pieris Pharmaceuticals Gmbh | Novel specific-binding polypeptides and uses thereof |
| JP7108535B2 (ja) | 2015-07-15 | 2022-07-28 | ピエリス ファーマシューティカルズ ゲーエムベーハー | Ｌａｇ－３に特異的な新規タンパク質 |
| CN113372446A (zh) * | 2016-06-08 | 2021-09-10 | 苏州康乃德生物医药有限公司 | 用于结合白细胞介素4受体的抗体 |
| KR20190104409A (ko) | 2017-01-18 | 2019-09-09 | 피어이스 파마슈티컬즈 게엠베하 | Lag-3에 대하여 결합 친화성을 갖는 리포칼린 뮤테인 |
| AU2018254542B2 (en) * | 2017-04-21 | 2022-12-22 | Elanco Us Inc. | IL4/IL13 receptor molecule for veterinary use |
| CN111494625B (zh) | 2018-12-25 | 2022-06-21 | 江苏荃信生物医药股份有限公司 | 用于治疗il-4和/或il-13介导的信号转导相关的疾病的药物组合物 |
| SG11202109839YA (en) | 2019-03-29 | 2021-10-28 | Astrazeneca Ab | Lipocalin mutein for treatment of asthma |
| CA3127973A1 (en) * | 2019-03-29 | 2020-10-08 | Pieris Pharmaceuticals Gmbh | Inhaled administration of lipocalin muteins |
| CR20230265A (es) | 2020-12-18 | 2023-09-29 | Astrazeneca Ab | Formulación de polvo seco de muteína de lipocalina para el tratamiento del asma |
| CN115414467B (zh) * | 2022-10-14 | 2023-06-06 | 中国人民解放军陆军军医大学第二附属医院 | 载脂蛋白d在制备治疗脑出血药物中的用途 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| DE4425255A1 (de) | 1994-07-16 | 1996-01-18 | Asta Medica Ag | Formulierung zur inhalativen Applikation |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| US6446467B1 (en) | 1997-07-29 | 2002-09-10 | Physical Optics Corporation | Monolithic glass light shaping diffuser and method for its production |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| KR20010052622A (ko) | 1998-06-08 | 2001-06-25 | 프리돌린 클라우스너, 롤란드 비. 보레르 | 만성 씨형 간염을 치료하기 위한 폴리에틸렌글리콜-인터페론-알파 및 리바비린의 용도 |
| US6403564B1 (en) | 1998-10-16 | 2002-06-11 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
| DE10043509A1 (de) | 2000-09-01 | 2002-03-14 | Asta Medica Ag | Feste Peptidzubereitungen für die Inhalation und deren Herstellung |
| US7211395B2 (en) | 2001-03-09 | 2007-05-01 | Dyax Corp. | Serum albumin binding moieties |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| AU2001298053A1 (en) | 2001-09-27 | 2003-04-14 | Pieris Proteolab Ag | Muteins of apolipoprotein D |
| AU2003233583A1 (en) * | 2002-05-24 | 2003-12-12 | Agennix Incorporated | Oral lactoferrin in the treatment of respiratory disorders |
| US7691970B2 (en) | 2003-08-25 | 2010-04-06 | Pieris Ag | Muteins of a bilin-binding protein with affinity for a given target |
| AU2003275958A1 (en) | 2003-08-25 | 2005-03-10 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| RU2389796C2 (ru) | 2003-08-29 | 2010-05-20 | Аэровэнс, Инк. | Модифицированный антагонист рецептора il-4 и предназначенный для его получения очищенный полинуклеотид |
| US7892827B2 (en) | 2004-11-26 | 2011-02-22 | Pieris Ag | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| WO2007038619A2 (en) | 2005-09-27 | 2007-04-05 | Amunix, Inc. | Proteinaceous pharmaceuticals and uses thereof |
| US8598317B2 (en) | 2006-03-20 | 2013-12-03 | Technische Universitaet Muenchen | Muteins of tear lipocalin with affinity for the T-cell coreceptor CD4 |
| JP5608368B2 (ja) | 2006-08-01 | 2014-10-15 | ピエリス アーゲー | 涙リポカリンの突然変異タンパク質およびそれを得るための方法 |
| KR20100047866A (ko) * | 2007-07-11 | 2010-05-10 | 애로반스, 인코포레이티드 | 약제학적 폴리펩타이드 건조 분말 에어로졸 제형 및 이의 제조 방법 |
| US8986951B2 (en) | 2010-06-08 | 2015-03-24 | Pieris Ag | Tear lipocalin in muteins binding IL-4 R alpha |
| TR201901826T4 (tr) | 2011-12-13 | 2019-03-21 | Astrazeneca Ab | Il-4 ve/veya ıl-13'ün ilgili reseptörlerine bağlanmasını inhibe ederek belirli rahatsızlıkların önlenmesi ya da tedavi edilmesi için yöntemler. |
-
2012
- 2012-12-12 TR TR2019/01826T patent/TR201901826T4/tr unknown
- 2012-12-12 ES ES18197286T patent/ES2863410T3/es active Active
- 2012-12-12 EP EP12813295.8A patent/EP2790719B1/en active Active
- 2012-12-12 PL PL18197286T patent/PL3453400T3/pl unknown
- 2012-12-12 HU HUE12813295A patent/HUE042720T2/hu unknown
- 2012-12-12 CA CA2858962A patent/CA2858962C/en active Active
- 2012-12-12 PL PL12813295T patent/PL2790719T3/pl unknown
- 2012-12-12 ES ES12813295T patent/ES2710384T3/es active Active
- 2012-12-12 EP EP21152253.7A patent/EP3842058B1/en active Active
- 2012-12-12 WO PCT/EP2012/075146 patent/WO2013087660A1/en not_active Ceased
- 2012-12-12 SG SG10201604566QA patent/SG10201604566QA/en unknown
- 2012-12-12 CN CN201811146540.5A patent/CN109432402B/zh not_active Expired - Fee Related
- 2012-12-12 DK DK18197286.0T patent/DK3453400T3/da active
- 2012-12-12 EP EP18197286.0A patent/EP3453400B1/en active Active
- 2012-12-12 CN CN201280061754.7A patent/CN103998053B9/zh not_active Expired - Fee Related
- 2012-12-12 SG SG11201402992SA patent/SG11201402992SA/en unknown
- 2012-12-12 US US14/364,449 patent/US9572863B2/en not_active Expired - Fee Related
- 2012-12-12 HU HUE18197286A patent/HUE054342T2/hu unknown
- 2012-12-12 DK DK12813295.8T patent/DK2790719T3/en active
- 2012-12-12 AU AU2012350660A patent/AU2012350660B2/en not_active Ceased
- 2012-12-12 JP JP2014546471A patent/JP6163162B2/ja not_active Expired - Fee Related
-
2016
- 2016-12-02 US US15/367,680 patent/US10016483B2/en active Active
-
2017
- 2017-03-30 JP JP2017067615A patent/JP6725447B2/ja not_active Expired - Fee Related
-
2018
- 2018-06-07 US US16/002,704 patent/US10398754B2/en active Active
-
2019
- 2019-03-28 JP JP2019062186A patent/JP6889201B2/ja not_active Expired - Fee Related
- 2019-07-16 US US16/513,636 patent/US10857202B2/en not_active Expired - Fee Related
-
2020
- 2020-05-27 JP JP2020092168A patent/JP2020164532A/ja active Pending
- 2020-11-05 US US17/090,571 patent/US11382951B2/en active Active
-
2022
- 2022-03-25 JP JP2022049676A patent/JP7441589B2/ja active Active
- 2022-06-14 US US17/839,635 patent/US20230021168A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11382951B2 (en) | Methods for preventing or treating certain disorders by inhibiting binding of IL-4 and/or IL-13 to their respective receptors | |
| Borthwick | The IL-1 cytokine family and its role in inflammation and fibrosis in the lung | |
| HK40051700A (en) | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors | |
| CN104394881A (zh) | 修饰的人肿瘤坏死因子受体-1多肽的新用途 | |
| HK40004111B (en) | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors | |
| HK40004111A (en) | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors | |
| HK40001660B (en) | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors | |
| HK40001660A (en) | Methods for preventing or treating certain disorders by inhibiting binding of il-4 and/or il-13 to their respective receptors | |
| CN106540242B (zh) | IL-1F7a的作用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20171124 |
|
| EEER | Examination request |
Effective date: 20171124 |
|
| EEER | Examination request |
Effective date: 20171124 |
|
| EEER | Examination request |
Effective date: 20171124 |
|
| EEER | Examination request |
Effective date: 20171124 |