DE69611766T2 - Spezifische Bindungspartner für menschliches TGF-beta, Materialien und Verfahren - Google Patents
Spezifische Bindungspartner für menschliches TGF-beta, Materialien und VerfahrenInfo
- Publication number
- DE69611766T2 DE69611766T2 DE69611766T DE69611766T DE69611766T2 DE 69611766 T2 DE69611766 T2 DE 69611766T2 DE 69611766 T DE69611766 T DE 69611766T DE 69611766 T DE69611766 T DE 69611766T DE 69611766 T2 DE69611766 T2 DE 69611766T2
- Authority
- DE
- Germany
- Prior art keywords
- antibody
- specific binding
- tgfβ
- tgfβ2
- domain
- 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.)
- Expired - Lifetime
Links
- 102000004887 Transforming Growth Factor beta Human genes 0.000 title claims abstract description 89
- 108090001012 Transforming Growth Factor beta Proteins 0.000 title claims abstract description 89
- 230000009870 specific binding Effects 0.000 title claims abstract description 87
- 238000000034 method Methods 0.000 title claims description 54
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 title abstract description 14
- 239000000463 material Substances 0.000 title description 9
- 230000008569 process Effects 0.000 title description 4
- 230000027455 binding Effects 0.000 claims abstract description 152
- 239000000427 antigen Substances 0.000 claims abstract description 69
- 108091007433 antigens Proteins 0.000 claims abstract description 57
- 102000036639 antigens Human genes 0.000 claims abstract description 57
- 230000000694 effects Effects 0.000 claims abstract description 46
- 108010029485 Protein Isoforms Proteins 0.000 claims abstract description 28
- 102000001708 Protein Isoforms Human genes 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 238000000338 in vitro Methods 0.000 claims abstract description 11
- 208000026278 immune system disease Diseases 0.000 claims abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims description 102
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 85
- 150000001413 amino acids Chemical class 0.000 claims description 40
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 31
- 238000006386 neutralization reaction Methods 0.000 claims description 28
- 150000007523 nucleic acids Chemical class 0.000 claims description 26
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 25
- 230000037390 scarring Effects 0.000 claims description 25
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 102000039446 nucleic acids Human genes 0.000 claims description 21
- 206010016654 Fibrosis Diseases 0.000 claims description 20
- 238000010494 dissociation reaction Methods 0.000 claims description 19
- 230000005593 dissociations Effects 0.000 claims description 19
- 229920001184 polypeptide Polymers 0.000 claims description 17
- 230000014509 gene expression Effects 0.000 claims description 16
- 230000004761 fibrosis Effects 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 238000007792 addition Methods 0.000 claims description 12
- 210000002540 macrophage Anatomy 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 8
- 206010038934 Retinopathy proliferative Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 206010039580 Scar Diseases 0.000 claims description 7
- 238000003780 insertion Methods 0.000 claims description 7
- 230000037431 insertion Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 6
- 206010038848 Retinal detachment Diseases 0.000 claims description 5
- 238000012217 deletion Methods 0.000 claims description 5
- 230000037430 deletion Effects 0.000 claims description 5
- 239000013604 expression vector Substances 0.000 claims description 5
- 230000004264 retinal detachment Effects 0.000 claims description 5
- 208000002177 Cataract Diseases 0.000 claims description 4
- 208000002260 Keloid Diseases 0.000 claims description 4
- 206010023330 Keloid scar Diseases 0.000 claims description 4
- 206010039710 Scleroderma Diseases 0.000 claims description 4
- 238000002399 angioplasty Methods 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 210000001117 keloid Anatomy 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- 230000001717 pathogenic effect Effects 0.000 claims description 4
- 208000019553 vascular disease Diseases 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 230000009931 harmful effect Effects 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 238000004113 cell culture Methods 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 230000001537 neural effect Effects 0.000 claims 4
- 208000031481 Pathologic Constriction Diseases 0.000 claims 2
- 230000007812 deficiency Effects 0.000 claims 2
- 230000036262 stenosis Effects 0.000 claims 2
- 208000037804 stenosis Diseases 0.000 claims 2
- 230000009429 distress Effects 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 201000003068 rheumatic fever Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 abstract description 27
- 238000011282 treatment Methods 0.000 abstract description 14
- 230000001225 therapeutic effect Effects 0.000 abstract description 7
- 230000003176 fibrotic effect Effects 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 3
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 abstract description 2
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 abstract description 2
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 abstract 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 66
- 238000002965 ELISA Methods 0.000 description 50
- 239000002953 phosphate buffered saline Substances 0.000 description 49
- 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 48
- 238000003556 assay Methods 0.000 description 45
- 235000001014 amino acid Nutrition 0.000 description 37
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 30
- 210000001519 tissue Anatomy 0.000 description 28
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 27
- 239000013598 vector Substances 0.000 description 27
- 108020004414 DNA Proteins 0.000 description 26
- 229940098773 bovine serum albumin Drugs 0.000 description 26
- 238000003752 polymerase chain reaction Methods 0.000 description 26
- 230000003321 amplification Effects 0.000 description 24
- 230000009260 cross reactivity Effects 0.000 description 24
- 238000003199 nucleic acid amplification method Methods 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 239000012634 fragment Substances 0.000 description 23
- 239000013615 primer Substances 0.000 description 21
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 108020003175 receptors Proteins 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 19
- 239000000047 product Substances 0.000 description 17
- 239000002609 medium Substances 0.000 description 16
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 210000004602 germ cell Anatomy 0.000 description 15
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 14
- 101500025614 Homo sapiens Transforming growth factor beta-1 Proteins 0.000 description 14
- 238000010790 dilution Methods 0.000 description 14
- 239000012895 dilution Substances 0.000 description 14
- 238000004091 panning Methods 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 230000004071 biological effect Effects 0.000 description 13
- 238000010276 construction Methods 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 13
- 210000005036 nerve Anatomy 0.000 description 13
- 210000002741 palatine tonsil Anatomy 0.000 description 13
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 12
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 12
- 108091034117 Oligonucleotide Proteins 0.000 description 12
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 11
- 101500025624 Homo sapiens Transforming growth factor beta-2 Proteins 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 239000002245 particle Substances 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- 208000027418 Wounds and injury Diseases 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 244000144725 Amygdalus communis Species 0.000 description 9
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 9
- 241000588724 Escherichia coli Species 0.000 description 9
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 9
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 239000000499 gel Substances 0.000 description 9
- 238000002823 phage display Methods 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 230000003389 potentiating effect Effects 0.000 description 9
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 8
- 241000283707 Capra Species 0.000 description 8
- 229920002307 Dextran Polymers 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 8
- 235000011437 Amygdalus communis Nutrition 0.000 description 7
- 102000016359 Fibronectins Human genes 0.000 description 7
- 108010067306 Fibronectins Proteins 0.000 description 7
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 238000002835 absorbance Methods 0.000 description 7
- 238000005273 aeration Methods 0.000 description 7
- 239000011543 agarose gel Substances 0.000 description 7
- 235000020224 almond Nutrition 0.000 description 7
- 229960000723 ampicillin Drugs 0.000 description 7
- 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 7
- 230000004663 cell proliferation Effects 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 7
- 238000004520 electroporation Methods 0.000 description 7
- 210000001508 eye Anatomy 0.000 description 7
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 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 6
- NKDFYOWSKOHCCO-YPVLXUMRSA-N 20-hydroxyecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)(O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 NKDFYOWSKOHCCO-YPVLXUMRSA-N 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 206010052428 Wound Diseases 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 238000002703 mutagenesis Methods 0.000 description 6
- 231100000350 mutagenesis Toxicity 0.000 description 6
- 229920000136 polysorbate Polymers 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 5
- 238000001712 DNA sequencing Methods 0.000 description 5
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
- 108010067902 Peptide Library Proteins 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 239000003593 chromogenic compound Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 238000012421 spiking Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 238000012408 PCR amplification Methods 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 108010059712 Pronase Proteins 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 108010006785 Taq Polymerase Proteins 0.000 description 4
- 239000004098 Tetracycline Substances 0.000 description 4
- 230000001028 anti-proliverative effect Effects 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000003636 conditioned culture medium Substances 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 238000000099 in vitro assay Methods 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000003118 sandwich ELISA Methods 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 229960002180 tetracycline Drugs 0.000 description 4
- 229930101283 tetracycline Natural products 0.000 description 4
- 235000019364 tetracycline Nutrition 0.000 description 4
- 150000003522 tetracyclines Chemical class 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241001244729 Apalis Species 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 3
- 208000036566 Erythroleukaemia Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 229920002527 Glycogen Polymers 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 101800001155 Latency-associated peptide Proteins 0.000 description 3
- 102400000401 Latency-associated peptide Human genes 0.000 description 3
- 108010014251 Muramidase Proteins 0.000 description 3
- 102000016943 Muramidase Human genes 0.000 description 3
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 206010036030 Polyarthritis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 208000021841 acute erythroid leukemia Diseases 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 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 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000000991 chicken egg Anatomy 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 229940096919 glycogen Drugs 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000010191 image analysis Methods 0.000 description 3
- 238000003365 immunocytochemistry Methods 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000004325 lysozyme Substances 0.000 description 3
- 229960000274 lysozyme Drugs 0.000 description 3
- 235000010335 lysozyme Nutrition 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000010807 negative regulation of binding Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 235000020183 skimmed milk Nutrition 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- 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 2
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 description 2
- 108010038061 Chymotrypsinogen Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 208000027219 Deficiency disease Diseases 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 102000002322 Egg Proteins Human genes 0.000 description 2
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 239000008156 Ringer's lactate solution Substances 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- -1 carrier Substances 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 235000014103 egg white Nutrition 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000028709 inflammatory response 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
- 230000000670 limiting effect Effects 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 239000006152 selective media Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 206010003162 Arterial injury Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101500025630 Bos taurus Transforming growth factor beta-2 Proteins 0.000 description 1
- 101000597784 Bos taurus Tumor necrosis factor Proteins 0.000 description 1
- 101100494773 Caenorhabditis elegans ctl-2 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 101100112369 Fasciola hepatica Cat-1 gene Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000662009 Homo sapiens UDP-N-acetylglucosamine pyrophosphorylase Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 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
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100206411 Mus musculus Tgfb2 gene Proteins 0.000 description 1
- 101500025613 Mus musculus Transforming growth factor beta-1 Proteins 0.000 description 1
- NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical compound O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 description 1
- 101100005271 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cat-1 gene Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 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
- 241000282887 Suidae Species 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102100037921 UDP-N-acetylglucosamine pyrophosphorylase Human genes 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- BMLSTPRTEKLIPM-UHFFFAOYSA-I calcium;potassium;disodium;hydrogen carbonate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].OC([O-])=O BMLSTPRTEKLIPM-UHFFFAOYSA-I 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000012502 diagnostic product Substances 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 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 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 108010021083 hen egg lysozyme Proteins 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940100602 interleukin-5 Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 210000003140 lateral ventricle Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- KUHRIIPUCPOQMQ-UHFFFAOYSA-N n,n-diethyl-3-(ethyliminomethylideneamino)propan-1-amine Chemical compound CCN=C=NCCCN(CC)CC KUHRIIPUCPOQMQ-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000024833 regulation of cytokine production Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.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 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P27/12—Ophthalmic agents for cataracts
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Biophysics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9520486.3A GB9520486D0 (en) | 1995-10-06 | 1995-10-06 | Specific binding members for human transforming growth factor beta; materials and methods |
| GBGB9601081.4A GB9601081D0 (en) | 1995-10-06 | 1996-01-19 | Specific binding members for human transforming growth factor beta;materials and methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69611766D1 DE69611766D1 (de) | 2001-03-15 |
| DE69611766T2 true DE69611766T2 (de) | 2001-08-02 |
Family
ID=26307896
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69611766T Expired - Lifetime DE69611766T2 (de) | 1995-10-06 | 1996-10-07 | Spezifische Bindungspartner für menschliches TGF-beta, Materialien und Verfahren |
| DE69607191T Expired - Lifetime DE69607191T2 (de) | 1995-10-06 | 1996-10-07 | Spezifische bindungspartner für menschlichen transformierenden wachstumsfaktor und verfahren |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69607191T Expired - Lifetime DE69607191T2 (de) | 1995-10-06 | 1996-10-07 | Spezifische bindungspartner für menschlichen transformierenden wachstumsfaktor und verfahren |
Country Status (12)
| Country | Link |
|---|---|
| EP (2) | EP0945464B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP4387458B2 (cg-RX-API-DMAC7.html) |
| AT (2) | ATE199091T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU702049B2 (cg-RX-API-DMAC7.html) |
| CA (2) | CA2599488A1 (cg-RX-API-DMAC7.html) |
| DE (2) | DE69611766T2 (cg-RX-API-DMAC7.html) |
| DK (2) | DK0853661T3 (cg-RX-API-DMAC7.html) |
| ES (2) | ES2156035T3 (cg-RX-API-DMAC7.html) |
| GB (2) | GB9601081D0 (cg-RX-API-DMAC7.html) |
| GR (2) | GR3033436T3 (cg-RX-API-DMAC7.html) |
| PT (2) | PT945464E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997013844A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (188)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6025154A (en) | 1995-06-06 | 2000-02-15 | Human Genome Sciences, Inc. | Polynucleotides encoding human G-protein chemokine receptor HDGNR10 |
| US7368111B2 (en) | 1995-10-06 | 2008-05-06 | Cambridge Antibody Technology Limited | Human antibodies specific for TGFβ2 |
| US7888466B2 (en) | 1996-01-11 | 2011-02-15 | Human Genome Sciences, Inc. | Human G-protein chemokine receptor HSATU68 |
| WO2000001410A1 (en) | 1998-07-06 | 2000-01-13 | Beth Israel Deaconess Medical Center | Methods of inhibiting proliferative diseases by inhibiting tgf-beta mediated angiogenesis |
| WO2000062062A1 (en) * | 1999-04-09 | 2000-10-19 | Hanmi Pharm Co., Ltd. | METHOD FOR QUANTIFYING TRANSFORMING GROWTH FACTOR-β1 AND METHOD FOR DETECTING CANCER BY USING SAME |
| US6492497B1 (en) * | 1999-04-30 | 2002-12-10 | Cambridge Antibody Technology Limited | Specific binding members for TGFbeta1 |
| EP1486560A3 (en) * | 1999-04-30 | 2005-02-09 | Cambridge Antibody Technology LTD | Specific antibodies and antibody fragments for TGFBETA1 |
| US7291714B1 (en) | 1999-06-30 | 2007-11-06 | Millennium Pharmaceuticals, Inc. | Glycoprotein VI and uses thereof |
| US20040001826A1 (en) | 1999-06-30 | 2004-01-01 | Millennium Pharmaceuticals, Inc. | Glycoprotein VI and uses thereof |
| AU7825500A (en) * | 1999-10-07 | 2001-04-23 | Pharmacia Corporation | Inhibition enzyme linked immunosorbent assay (iELISA) for the detection and quantification of antibodies in biological samples |
| SE9903895D0 (sv) * | 1999-10-28 | 1999-10-28 | Active Biotech Ab | Novel compounds |
| WO2002043660A2 (en) | 2000-11-28 | 2002-06-06 | Mediummune, Inc | Methods of administering/dosing anti-rsv antibodies for prophylaxis and treatment |
| WO2002002641A1 (en) | 2000-06-16 | 2002-01-10 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to blys |
| EP1339847A2 (en) * | 2000-11-28 | 2003-09-03 | Amgen, Inc. | Transforming growth factor-beta-related molecules and uses thereof |
| US7175988B2 (en) | 2001-02-09 | 2007-02-13 | Human Genome Sciences, Inc. | Human G-protein Chemokine Receptor (CCR5) HDGNR10 |
| CN1564826A (zh) * | 2001-02-09 | 2005-01-12 | 人类基因组科学公司 | 人类g蛋白趋化因子受体(ccr5)hdgnr10 |
| WO2002083704A1 (en) | 2001-04-13 | 2002-10-24 | Human Genome Sciences, Inc. | Vascular endothelial growth factor 2 |
| ES2437992T3 (es) | 2001-05-25 | 2014-01-15 | Human Genome Sciences, Inc. | Anticuerpos que se unen inmunoespecíficamente a los receptores de TRAIL |
| US7393934B2 (en) | 2001-12-21 | 2008-07-01 | Human Genome Sciences, Inc. | Human G-protein chemokine receptor (CCR5) HDGNR10 |
| DE10210427A1 (de) | 2002-03-09 | 2003-10-09 | Hans Konrad Mueller-Hermelink | Humaner monoklonaler Antikörper |
| WO2003086458A1 (en) | 2002-04-12 | 2003-10-23 | Medimmune, Inc. | Recombinant anti-interleukin-9 antibodies |
| JP4643255B2 (ja) | 2002-06-10 | 2011-03-02 | バクシネックス インコーポレーティッド | 乳癌および膀胱癌において差次的に発現される遺伝子ならびにコードされるポリペプチド |
| US7425618B2 (en) | 2002-06-14 | 2008-09-16 | Medimmune, Inc. | Stabilized anti-respiratory syncytial virus (RSV) antibody formulations |
| AU2003249533A1 (en) | 2002-07-04 | 2004-01-23 | Oncomab Gmbh | Neoplasm specific antibodies and uses thereof |
| DK2891666T3 (en) | 2002-10-16 | 2017-10-02 | Purdue Pharma Lp | Antibodies that bind cell-associated CA 125 / O722P and methods for its use |
| GB0224436D0 (en) * | 2002-10-21 | 2002-11-27 | Univ Cambridge Tech | Polypetides methods and means |
| JP4511943B2 (ja) * | 2002-12-23 | 2010-07-28 | ワイス エルエルシー | Ｐｄ−１に対する抗体およびその使用 |
| DE10311248A1 (de) | 2003-03-14 | 2004-09-30 | Müller-Hermelink, Hans Konrad, Prof. Dr. | Humaner monoklonaler Antikörper |
| JP4764818B2 (ja) | 2003-04-11 | 2011-09-07 | メディミューン，エルエルシー | 組換えｉｌ−９抗体およびその使用 |
| CA2525647A1 (en) | 2003-05-16 | 2005-02-24 | Intermune, Inc. | Synthetic chemokine receptor ligands and methods of use thereof |
| WO2005010049A2 (en) * | 2003-07-09 | 2005-02-03 | Eli Lilly And Company | Tgf-beta1 ligands |
| US7393534B2 (en) | 2003-07-15 | 2008-07-01 | Barros Research Institute | Compositions and methods for immunotherapy of cancer and infectious diseases |
| EP2133362B1 (en) | 2003-07-25 | 2012-04-18 | Amgen, Inc | Methods relating to LDCAM and CRTAM |
| WO2005014795A2 (en) | 2003-08-08 | 2005-02-17 | Genenews Inc. | Osteoarthritis biomarkers and uses thereof |
| DE10353175A1 (de) | 2003-11-14 | 2005-06-16 | Müller-Hermelink, Hans Konrad, Prof. Dr. | Humaner monoklonaler Antikörper mit fettsenkender Wirkung |
| EP1531162A1 (en) | 2003-11-14 | 2005-05-18 | Heinz Vollmers | Adenocarcinoma specific antibody SAM-6, and uses thereof |
| EP1723178A4 (en) | 2004-03-12 | 2007-12-12 | Human Genome Sciences Inc | HUMAN G-PROTEIN CHEMOKIN RECEPTOR (CCR5) HDGNR10 |
| WO2005097832A2 (en) | 2004-03-31 | 2005-10-20 | Genentech, Inc. | Humanized anti-tgf-beta antibodies |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| JP2008513540A (ja) | 2004-09-21 | 2008-05-01 | メディミューン，インコーポレーテッド | 呼吸器合胞体ウイルスに対する抗体及び該ウイルス用のワクチンを製造する方法 |
| JP2008518023A (ja) | 2004-10-27 | 2008-05-29 | メディミューン，インコーポレーテッド | 同族抗原に対する親和性を改変することによる抗体特異性の調節 |
| CN103497993A (zh) | 2005-02-07 | 2014-01-08 | 基因信息公司 | 轻度骨关节炎生物标志物及其用途 |
| TR201901929T4 (tr) | 2005-02-08 | 2019-03-21 | Genzyme Corp | TGFBeta'ya antikorlar. |
| DK1853718T3 (en) | 2005-02-15 | 2015-11-09 | Univ Duke | ANTI-CD19 ANTIBODIES AND THEIR USE IN ONCOLOGY |
| WO2006096565A2 (en) | 2005-03-04 | 2006-09-14 | Curedm Inc. | Methods and pharmaceutical compositions for treating type 1 diabetes mellitus and other conditions |
| PL1874818T3 (pl) | 2005-04-22 | 2011-09-30 | Lilly Co Eli | Przeciwciała swoiste wobec TGF-beta 1 |
| AU2006244445B2 (en) | 2005-05-05 | 2013-04-18 | Duke University | Anti-CD19 antibody therapy for autoimmune disease |
| WO2006128083A2 (en) | 2005-05-25 | 2006-11-30 | Curedm, Inc. | Human proislet peptide, derivatives and analogs thereof, and methods of using same |
| WO2007002543A2 (en) | 2005-06-23 | 2007-01-04 | Medimmune, Inc. | Antibody formulations having optimized aggregation and fragmentation profiles |
| WO2007048074A1 (en) | 2005-10-21 | 2007-04-26 | Genenews Inc. | Method and apparatus for correlating levels of biomarker products with disease |
| US8597646B2 (en) | 2005-10-25 | 2013-12-03 | The Johns Hopkins University | Methods and compositons featuring TGF-beta antagonists for the treatment of marfan syndrome and associated disorders |
| WO2007103469A2 (en) | 2006-03-06 | 2007-09-13 | Aeres Biomedical Ltd. | Humanized anti-cd22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
| WO2007108992A2 (en) | 2006-03-13 | 2007-09-27 | The Johns Hopkins University | Augmentation of endothelial thromboresistance |
| SG10201504662WA (en) | 2006-06-14 | 2015-07-30 | Macrogenics Inc | Methods For The Treatment Of Autoimmune Disorders Using Immunosuppressive Monoclonal Antibodies With Reduced Toxicity |
| TWI405771B (zh) | 2006-08-28 | 2013-08-21 | Kyowa Hakko Kirin Co Ltd | 具拮抗性之人類ｌｉｇｈｔ專一性人類單株抗體 |
| EP2083863B1 (en) | 2006-10-03 | 2015-03-18 | Genzyme Corporation | Antibodies to tgf-beta for use in the treatment of infants at risk of developing bronchopulmonary dysplasia |
| US8785400B2 (en) | 2006-11-22 | 2014-07-22 | Curedm Group Holdings, Llc | Methods and compositions relating to islet cell neogenesis |
| CN101678100A (zh) | 2006-12-06 | 2010-03-24 | 米迪缪尼有限公司 | 治疗系统性红斑狼疮的方法 |
| JP5456658B2 (ja) | 2007-03-30 | 2014-04-02 | メディミューン，エルエルシー | 抗体製剤 |
| RU2549701C2 (ru) | 2007-05-07 | 2015-04-27 | Медиммун, Ллк | Анти-icos антитела и их применение в лечении онкологических, связанных с трансплантацией и аутоиммунных заболеваний |
| PT2068927E (pt) | 2007-05-14 | 2016-02-10 | Medimmune Llc | Métodos para reduzir os níveis de eosinófilos |
| NZ599756A (en) | 2007-08-30 | 2013-09-27 | Curedm Group Holdings Llc | Compositions and methods of using proislet peptides and analogs thereof |
| WO2009061818A1 (en) | 2007-11-05 | 2009-05-14 | Medimmune, Llc | Methods of treating scleroderma |
| WO2009070642A1 (en) | 2007-11-28 | 2009-06-04 | Medimmune, Llc | Protein formulation |
| US20110033378A1 (en) | 2008-01-18 | 2011-02-10 | Medlmmune, Llc. | Cysteine Engineered Antibodies For Site-Specific Conjugation |
| EP2250279B1 (en) | 2008-02-08 | 2016-04-13 | MedImmune, LLC | Anti-ifnar1 antibodies with reduced fc ligand affinity |
| CN103483450B (zh) | 2008-10-31 | 2015-11-25 | 东丽株式会社 | 抗人cxcl1单克隆抗体或其片段 |
| ES2719496T3 (es) | 2008-11-12 | 2019-07-10 | Medimmune Llc | Formulación de anticuerpo |
| EP2387584A1 (en) | 2009-01-14 | 2011-11-23 | IQ Therapeutics BV | Combination antibodies for the treatment and prevention of disease caused by bacillus anthracis and related bacteria and their toxins |
| US8852608B2 (en) | 2009-02-02 | 2014-10-07 | Medimmune, Llc | Antibodies against and methods for producing vaccines for respiratory syncytial virus |
| JP5918129B2 (ja) | 2009-06-22 | 2016-05-18 | メディミューン，エルエルシー | 部位特異的共役のための操作されたＦｃ領域 |
| JP5762408B2 (ja) | 2009-08-13 | 2015-08-12 | クルセル ホランド ベー ヴェー | ヒト呼吸器合胞体ウイルス（ｒｓｖ）に対する抗体および使用方法 |
| JP2013509874A (ja) | 2009-11-04 | 2013-03-21 | エラスムス ユニバーシティ メディカル センター ロッテルダム | 新脈管形成を調節する為の新規化合物及びこれらの化合物を使用する処置方法 |
| PT2835053T (pt) | 2010-03-12 | 2016-07-14 | Genzyme Corp | Terapêutica combinada para o tratamento do cancro da mama |
| CN103097412B (zh) | 2010-07-09 | 2016-08-10 | 克鲁塞尔荷兰公司 | 抗人呼吸道合胞病毒(rsv)抗体以及使用方法 |
| KR20130131414A (ko) | 2010-12-27 | 2013-12-03 | 엘에스아이피 환도 운에이고우도우가이샤 | ｉＰＳ 세포와 그 제조법 |
| WO2012103165A2 (en) | 2011-01-26 | 2012-08-02 | Kolltan Pharmaceuticals, Inc. | Anti-kit antibodies and uses thereof |
| EP2737083A1 (en) | 2011-07-27 | 2014-06-04 | INSERM (Institut National de la Santé et de la Recherche Scientifique) | Methods for diagnosing and treating myhre syndrome |
| MX2014004994A (es) | 2011-10-26 | 2014-08-27 | Seattle Children S Res Inst | Cisteamina en el tratamiento de enfermedad fibrotica. |
| WO2013078286A1 (en) | 2011-11-22 | 2013-05-30 | Cornell University | Methods for stimulating hematopoietic recovery by inhibiting tgf beta signaling |
| CA3111357A1 (en) | 2011-12-23 | 2013-06-27 | Pfizer Inc. | Engineered antibody constant regions for site-specific conjugation and methods and uses therefor |
| ES2917222T3 (es) | 2011-12-28 | 2022-07-07 | Kyoto Prefectural Public Univ Corp | Normalización del cultivo de células endoteliales de la córnea |
| AR092745A1 (es) | 2012-10-01 | 2015-04-29 | Univ Pennsylvania | Composiciones que comprenden un dominio de union anti-fap y metodos para hacer blanco en celulas estromales para el tratamiento del cancer |
| US9821010B2 (en) | 2013-02-07 | 2017-11-21 | The General Hospital Corporation | Methods for expansion or depletion of T-regulatory cells |
| WO2014129895A1 (en) | 2013-02-19 | 2014-08-28 | Stichting Vu-Vumc | Means and method for increasing the sensitivity of cancers for radiotherapy |
| HUE042020T2 (hu) * | 2013-03-11 | 2019-06-28 | Genzyme Corp | Génmódosított anti-TGF-béta ellenanyagok és antigénkötõ fragmensek |
| PT3702443T (pt) | 2013-03-14 | 2022-02-17 | Massachusetts Inst Technology | Composições e métodos para expansão e cultura de células estaminais epiteliais |
| CA2914369C (en) | 2013-06-06 | 2023-02-14 | Igenica Biotherapeutics, Inc. | Anti-c10orf54 antibodies and uses thereof |
| CA2914924A1 (en) | 2013-06-13 | 2014-12-18 | Fast Forward Pharmaceuticals B.V. | Cd40 signalling inhibitor and a further compound, wherein the further compound is a bile acid, a bile acid derivative, an tgr5-receptor agonist, an fxr agonist or a combination thereof, for the treatment of chronic inflammation, and the prevention of gastrointestinal cancer or fibrosis. |
| RS62189B1 (sr) | 2013-08-26 | 2021-08-31 | Biontech Research And Development Inc | Nukleinske kiseline koje kodiraju humana antitela na sijalil-luis a |
| WO2015050107A1 (ja) | 2013-10-01 | 2015-04-09 | 東レ株式会社 | 膵腫瘍の検出方法、抗体及び膵腫瘍検出用キット |
| RU2712967C2 (ru) | 2013-10-31 | 2020-02-03 | Киото Прифекчурал Паблик Юниверсити Корпорэйшн | Терапевтическое средство против заболеваний, связанных с гибелью клеток эндотелия роговицы, обусловленной состоянием эндоплазматического ретикулума |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| RS61678B1 (sr) | 2014-05-28 | 2021-05-31 | Agenus Inc | Anti-gitr antitela i postupci za njihovu primenu |
| EP3868405A1 (en) | 2014-06-04 | 2021-08-25 | BioNTech Research and Development, Inc. | Human monoclonal antibodies to ganglioside gd2 |
| CA2959404A1 (en) | 2014-09-03 | 2016-03-10 | The Brigham And Women's Hospital, Inc. | Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss |
| EP3201235A1 (en) | 2014-10-01 | 2017-08-09 | Medimmune Limited | Antibodies to ticagrelor and methods of use |
| KR102693806B1 (ko) | 2014-12-11 | 2024-08-09 | 피에르 파브르 메디카먼트 | 항-c10orf54 항체들 및 그들의 용도들 |
| ES2862701T3 (es) | 2014-12-22 | 2021-10-07 | Univ Rockefeller | Anticuerpos agonistas anti-MERTK y usos de los mismos |
| JP6677655B2 (ja) | 2015-01-26 | 2020-04-08 | 東レ株式会社 | 胆道癌の検出方法及び胆道癌検出用キット |
| DK3267197T3 (da) | 2015-03-02 | 2020-10-12 | Toray Industries | Fremgangsmåde og kit til detektionen af pankreatisk dysfunktion |
| LT3265123T (lt) | 2015-03-03 | 2023-01-25 | Kymab Limited | Antikūnai, naudojimas ir būdai |
| MY189692A (en) | 2015-05-07 | 2022-02-26 | Memorial Sloan Kettering Cancer Center | Anti-ox40 antibodies and methods of use thereof |
| EP3447075B1 (en) | 2015-05-15 | 2023-08-09 | The General Hospital Corporation | Antagonistic anti-tumor necrosis factor receptor superfamily antibodies |
| US10882903B2 (en) | 2015-05-18 | 2021-01-05 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Methods and compositions for treating an alphavirus infection |
| RS60792B1 (sr) | 2015-05-29 | 2020-10-30 | Agenus Inc | Anti-ctla-4 antitela i postupci za njihovu primenu |
| US20190135929A1 (en) | 2015-08-28 | 2019-05-09 | The General Hospital Corporation | Agonistic anti-tumor necrosis factor receptor 2 antibodies |
| AU2016317915B2 (en) | 2015-09-01 | 2021-02-18 | Agenus Inc. | Anti-PD-1 antibodies and methods of use thereof |
| WO2017120543A1 (en) | 2016-01-08 | 2017-07-13 | Massachusetts Institute Of Technology | Production of differentiated enteroendocrine cells and insulin producing cells |
| AU2017219254B2 (en) * | 2016-02-17 | 2019-12-12 | Novartis Ag | TGFbeta 2 antibodies |
| US10213511B2 (en) | 2016-03-02 | 2019-02-26 | Frequency Therapeutics, Inc. | Thermoreversible compositions for administration of therapeutic agents |
| US10201540B2 (en) | 2016-03-02 | 2019-02-12 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I |
| US11260130B2 (en) | 2016-03-02 | 2022-03-01 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV |
| DK3365368T3 (da) * | 2016-03-11 | 2023-06-26 | Scholar Rock Inc | Tgfbeta1-bindende immunoglobuliner og anvendelse deraf |
| KR102745778B1 (ko) | 2016-05-13 | 2024-12-24 | 더 제너럴 하스피탈 코포레이션 | 길항성 항-종양 괴사 인자 수용체 슈퍼패밀리 항체 |
| EP3458608B1 (en) | 2016-05-17 | 2025-07-23 | F. Hoffmann-La Roche AG | Stromal gene signatures for diagnosis and use in immunotherapy |
| NZ749355A (en) | 2016-05-27 | 2023-04-28 | Agenus Inc | Anti-tim-3 antibodies and methods of use thereof |
| CA3030099A1 (en) | 2016-07-08 | 2018-01-11 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
| TWI843168B (zh) | 2016-10-11 | 2024-05-21 | 美商艾吉納斯公司 | 抗ｌａｇ－３抗體及其使用方法 |
| EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| JP7045724B2 (ja) | 2016-11-07 | 2022-04-01 | ニューラクル サイエンス カンパニー リミテッド | 配列類似性を持つ抗ファミリー１９、メンバーａ５抗体及びその用途 |
| EP3551225A1 (en) | 2016-12-07 | 2019-10-16 | Agenus Inc. | Antibodies and methods of use thereof |
| MD3551660T2 (ro) | 2016-12-07 | 2024-03-31 | Agenus Inc | Anticorpi anti-CTLA-4 și procedee de utilizare a acestora |
| SG10201910821XA (en) | 2016-12-30 | 2020-01-30 | Frequency Therapeutics Inc | 1h-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells |
| AR110755A1 (es) | 2017-01-20 | 2019-05-02 | Genzyme Corp | Anticuerpos dirigidos a hueso |
| TW202506185A (zh) | 2017-01-20 | 2025-02-16 | 法商賽諾菲公司 | 抗TGF-β抗體及其用途 |
| JP7297672B2 (ja) | 2017-04-13 | 2023-06-26 | アジェナス インコーポレイテッド | 抗ｃｄ１３７抗体およびその使用方法 |
| WO2018193427A1 (en) | 2017-04-21 | 2018-10-25 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
| SMT202300243T1 (it) | 2017-05-01 | 2023-11-13 | Agenus Inc | Anticorpi anti-tigit e relativi metodi d'uso |
| JOP20190256A1 (ar) | 2017-05-12 | 2019-10-28 | Icahn School Med Mount Sinai | فيروسات داء نيوكاسل واستخداماتها |
| AU2018291082B2 (en) | 2017-06-27 | 2025-05-29 | Neuracle Science Co., Ltd. | Anti-FAM19A5 antibodies and uses thereof |
| CA3070774A1 (en) | 2017-08-25 | 2019-02-28 | Five Prime Therapeutics, Inc. | B7-h4 antibodies and methods of use thereof |
| US11707522B2 (en) | 2017-10-13 | 2023-07-25 | Boehringer Ingelheim International Gmbh | Human antibodies to Tn antigen |
| CN111315772A (zh) | 2017-10-31 | 2020-06-19 | 斯塔顿生物技术有限公司 | 抗apoc3抗体及其使用方法 |
| JP7544597B2 (ja) | 2017-11-06 | 2024-09-03 | ジェネンテック， インコーポレイテッド | がんの診断及び療法 |
| MX2020005473A (es) | 2017-11-27 | 2020-08-27 | Purdue Pharma Lp | Anticuerpos humanizados que se dirigen al factor tisular humano. |
| CA3091174A1 (en) | 2018-02-21 | 2019-08-29 | Five Prime Therapeutics, Inc. | B7-h4 antibody formulations |
| EA202091810A1 (ru) | 2018-03-02 | 2021-01-29 | Файв Прайм Терапьютикс, Инк. | Антитела к b7-h4 и способы их применения |
| CN119569873A (zh) | 2018-05-10 | 2025-03-07 | 纽洛可科学有限公司 | 抗序列相似家族19成员a5的抗体及其使用方法 |
| EP3814376B1 (en) | 2018-06-26 | 2025-09-03 | Mor Research Applications Ltd. | Transthyretin antibodies and uses thereof |
| MX2021000786A (es) | 2018-07-20 | 2021-06-15 | Pf Medicament | Receptor para supresor de ig del dominio v de activación de células t (vista). |
| WO2020037215A1 (en) | 2018-08-17 | 2020-02-20 | Icahn School Of Medicine At Mount Sinai | Recombinant newcastle disease viruses and uses thereof for the prevention of rsv disease or human metapneumovirus disease |
| US11617745B2 (en) | 2018-08-17 | 2023-04-04 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by downregulating FOXO |
| US11162071B2 (en) | 2018-08-17 | 2021-11-02 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by upregulating JAG-1 |
| WO2020065594A1 (en) | 2018-09-28 | 2020-04-02 | Kyowa Kirin Co., Ltd. | Il-36 antibodies and uses thereof |
| EP3860713A2 (en) | 2018-10-03 | 2021-08-11 | Staten Biotechnology B.V. | Antibodies specific for human and cynomolgus apoc3 and methods of use thereof |
| AU2019402163A1 (en) | 2018-12-20 | 2021-07-08 | Kyowa Kirin Co., Ltd. | Fn14 antibodies and uses thereof |
| SG11202104217QA (en) | 2019-01-02 | 2021-05-28 | Neuracle Science Co Ltd | Anti-family with sequence similarity 19, member a5 antibodies and method of use thereof |
| MX2021010003A (es) | 2019-02-26 | 2021-12-10 | Inspirna Inc | Anticuerpos anti-mertk de alta afinidad y usos de los mismos. |
| EP3947442A2 (en) | 2019-03-28 | 2022-02-09 | Danisco US Inc. | Engineered antibodies |
| EP3947737A2 (en) | 2019-04-02 | 2022-02-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of predicting and preventing cancer in patients having premalignant lesions |
| AU2020329217A1 (en) | 2019-08-12 | 2022-07-28 | Aptevo Research And Development Llc | 4-1BB and OX40 binding proteins and related compositions and methods, antibodies against 4-1BB, antibodies against OX40 |
| AU2020335928A1 (en) | 2019-08-30 | 2022-02-17 | Agenus Inc. | Anti-CD96 antibodies and methods of use thereof |
| AU2020342910A1 (en) | 2019-09-04 | 2022-04-07 | Pierre Fabre Medicament | Anti-VSIG4 antibody or antigen binding fragment and uses thereof |
| CN112852738B (zh) * | 2019-11-27 | 2023-02-28 | 四川省肿瘤医院 | 一种前列腺癌细胞膜片的制备方法 |
| EP4106788A1 (en) | 2020-02-18 | 2022-12-28 | Alector LLC | Pilra antibodies and methods of use thereof |
| KR20220151195A (ko) | 2020-03-06 | 2022-11-14 | 오엔에이 테라퓨틱스 에스.엘. | 항-cd36 항체 및 암을 치료하기 위한 이의 용도 |
| MX2022011892A (es) | 2020-03-26 | 2022-10-18 | Univ Vanderbilt | Anticuerpos monoclonales humanos dirigidos contra el coronavirus 2 del sindrome respiratorio agudo grave (sars-cov-2). |
| WO2021202473A2 (en) | 2020-03-30 | 2021-10-07 | Danisco Us Inc | Engineered antibodies |
| WO2021233834A1 (en) | 2020-05-17 | 2021-11-25 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of selecting and using the same |
| EP4182343A2 (en) | 2020-07-20 | 2023-05-24 | AstraZeneca UK Limited | Sars-cov-2 proteins, anti-sars-cov-2 antibodies, and methods of using the same |
| PE20231187A1 (es) | 2020-08-18 | 2023-08-15 | Cephalon Llc | Anticuerpos anti-par-2 y metodos de uso de los mismos |
| US20230382978A1 (en) | 2020-10-15 | 2023-11-30 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Antibody specific for sars-cov-2 receptor binding domain and therapeutic methods |
| WO2022087274A1 (en) | 2020-10-21 | 2022-04-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibodies that neutralize type-i interferon (ifn) activity |
| AU2021390501A1 (en) | 2020-12-01 | 2023-06-29 | Aptevo Research And Development Llc | Heterodimeric psma and cd3-binding bispecific antibodies |
| WO2022184853A1 (en) | 2021-03-03 | 2022-09-09 | Pierre Fabre Medicament | Anti-vsig4 antibody or antigen binding fragment and uses thereof |
| CA3214633A1 (en) | 2021-03-24 | 2022-09-29 | Toray Industries, Inc. | Method and kit for assisting in determination of malignant pancreatic cystic tumor |
| WO2022251446A1 (en) | 2021-05-28 | 2022-12-01 | Alexion Pharmaceuticals, Inc. | Methods for detecting cm-tma biomarkers |
| IL309349A (en) | 2021-06-14 | 2024-02-01 | argenx BV | Antibodies against interleukin 9 and methods of using them |
| IL309934A (en) | 2021-07-30 | 2024-03-01 | Ona Therapeutics S L | Anti-cd36 antibodies and their use to treat cancer |
| WO2023080900A1 (en) | 2021-11-05 | 2023-05-11 | Genentech, Inc. | Methods and compositions for classifying and treating kidney cancer |
| TW202342510A (zh) | 2022-02-18 | 2023-11-01 | 英商Ｒｑ生物科技有限公司 | 抗體 |
| WO2023192436A1 (en) | 2022-03-31 | 2023-10-05 | Alexion Pharmaceuticals, Inc. | Singleplex or multiplexed assay for complement markers in fresh biological samples |
| EP4514842A1 (en) | 2022-04-29 | 2025-03-05 | AstraZeneca UK Limited | Sars-cov-2 antibodies and methods of using the same |
| EP4536836A1 (en) | 2022-06-07 | 2025-04-16 | Regeneron Pharmaceuticals, Inc. | Pseudotyped viral particles for targeting tcr-expressing cells |
| WO2024015953A1 (en) | 2022-07-15 | 2024-01-18 | Danisco Us Inc. | Methods for producing monoclonal antibodies |
| WO2024013727A1 (en) | 2022-07-15 | 2024-01-18 | Janssen Biotech, Inc. | Material and methods for improved bioengineered pairing of antigen-binding variable regions |
| EP4583911A1 (en) | 2022-09-06 | 2025-07-16 | Alexion Pharmaceuticals, Inc. | Diagnostic and prognostic biomarker profiles in patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (hsct-tma) |
| WO2024077166A1 (en) | 2022-10-05 | 2024-04-11 | Genentech, Inc. | Methods and compositions for classifying and treating lung cancer |
| EP4599089A1 (en) | 2022-10-05 | 2025-08-13 | Genentech, Inc. | Methods and compositions for classifying and treating bladder cancer |
| AU2024240129A1 (en) | 2023-03-17 | 2025-10-09 | Oxitope Pharma B.V. | Anti-phosphocholine antibodies and methods of use thereof |
| WO2024194685A2 (en) | 2023-03-17 | 2024-09-26 | Oxitope Pharma B.V. | Anti-phosphocholine antibodies and methods of use thereof |
| AU2024277678A1 (en) | 2023-05-25 | 2025-11-27 | Dispatch Biotherapeutics, Inc. | Synthetic cancer antigens as targets for treating cancers |
| WO2025072888A2 (en) | 2023-09-28 | 2025-04-03 | Novavax, Inc. | Anti-sars-cov-2 spike (s) antibodies and their use in treating covid-19 |
| WO2025133707A1 (en) | 2023-12-19 | 2025-06-26 | Vectory Therapeutics B.V. | Anti-tdp-43 antibodies and uses thereof |
| WO2025171383A2 (en) | 2024-02-09 | 2025-08-14 | Dispatch Biotherapeutics, Inc. | Engineered cancer antigens and related methods and uses |
| WO2025171388A1 (en) | 2024-02-09 | 2025-08-14 | Dispatch Biotherapeutics, Inc. | Engineered cancer antigens with modified domains and related methods and uses |
| US20250361297A1 (en) | 2024-03-12 | 2025-11-27 | Adaptam Therapeutics, S.L. | Anti- siglec-15 binding molecules and methods of use |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1539188A (en) * | 1987-05-04 | 1988-11-10 | Bristol-Myers Squibb Company | TGF-B2 and novel compositions having anti-neoplastic activity |
| US5571714A (en) * | 1988-12-22 | 1996-11-05 | Celtrix Pharmaceuticals, Inc. | Monoclonal antibodies which bind both transforming growth factors β1 and β2 and methods of use |
| EP0494264B1 (en) * | 1989-09-29 | 1997-06-18 | La Jolla Cancer Research Foundation | Inhibiting transforming growth factor to prevent accumulation of extracellular matrix |
| GB9106678D0 (en) * | 1991-03-28 | 1991-05-15 | Ferguson Mark W J | Wound healing |
| DK0590058T3 (da) * | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
| WO1993011236A1 (en) * | 1991-12-02 | 1993-06-10 | Medical Research Council | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
| WO1993021945A1 (en) * | 1992-04-23 | 1993-11-11 | The Regents Of The University Of California | METHODS FOR TREATING VASCULAR DISORDERS BY INHIBITING THE ENDOTHELIN STIMULATORY ACTIVITY OF TGF$g(b) |
| JP3720353B2 (ja) * | 1992-12-04 | 2005-11-24 | メディカル リサーチ カウンシル | 多価および多重特異性の結合タンパク質、それらの製造および使用 |
| GB2288118A (en) * | 1994-03-29 | 1995-10-11 | Univ Manchester | Wound healing composition |
| DE69513158T2 (de) * | 1994-03-29 | 2000-05-04 | The Victoria University Of Manchester, Manchester | Wundheilung |
-
1996
- 1996-01-19 GB GBGB9601081.4A patent/GB9601081D0/en active Pending
- 1996-10-07 EP EP99102166A patent/EP0945464B1/en not_active Expired - Lifetime
- 1996-10-07 PT PT99102166T patent/PT945464E/pt unknown
- 1996-10-07 AT AT99102166T patent/ATE199091T1/de not_active IP Right Cessation
- 1996-10-07 GB GB9620920A patent/GB2305921B/en not_active Expired - Fee Related
- 1996-10-07 EP EP96932730A patent/EP0853661B1/en not_active Expired - Lifetime
- 1996-10-07 DK DK96932730T patent/DK0853661T3/da active
- 1996-10-07 CA CA002599488A patent/CA2599488A1/en not_active Abandoned
- 1996-10-07 JP JP51480997A patent/JP4387458B2/ja not_active Expired - Lifetime
- 1996-10-07 WO PCT/GB1996/002450 patent/WO1997013844A1/en not_active Ceased
- 1996-10-07 PT PT96932730T patent/PT853661E/pt unknown
- 1996-10-07 DE DE69611766T patent/DE69611766T2/de not_active Expired - Lifetime
- 1996-10-07 ES ES99102166T patent/ES2156035T3/es not_active Expired - Lifetime
- 1996-10-07 DE DE69607191T patent/DE69607191T2/de not_active Expired - Lifetime
- 1996-10-07 CA CA002233042A patent/CA2233042C/en not_active Expired - Fee Related
- 1996-10-07 DK DK99102166T patent/DK0945464T3/da active
- 1996-10-07 ES ES96932730T patent/ES2146020T3/es not_active Expired - Lifetime
- 1996-10-07 AT AT96932730T patent/ATE190650T1/de active
- 1996-10-07 AU AU71405/96A patent/AU702049B2/en not_active Ceased
-
2000
- 2000-05-18 GR GR20000401123T patent/GR3033436T3/el unknown
-
2001
- 2001-04-20 GR GR20010400625T patent/GR3035775T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997013844A1 (en) | 1997-04-17 |
| AU7140596A (en) | 1997-04-30 |
| EP0945464B1 (en) | 2001-02-07 |
| GB9601081D0 (en) | 1996-03-20 |
| DK0945464T3 (da) | 2001-05-07 |
| CA2599488A1 (en) | 1997-04-17 |
| AU702049B2 (en) | 1999-02-11 |
| ATE199091T1 (de) | 2001-02-15 |
| GB9620920D0 (en) | 1996-11-27 |
| GR3033436T3 (en) | 2000-09-29 |
| EP0853661B1 (en) | 2000-03-15 |
| CA2233042A1 (en) | 1997-04-17 |
| ES2146020T3 (es) | 2000-07-16 |
| DE69607191T2 (de) | 2000-09-28 |
| DK0853661T3 (da) | 2000-08-14 |
| PT945464E (pt) | 2001-07-31 |
| GR3035775T3 (en) | 2001-07-31 |
| DE69611766D1 (de) | 2001-03-15 |
| DE69607191D1 (de) | 2000-04-20 |
| ATE190650T1 (de) | 2000-04-15 |
| EP0945464A1 (en) | 1999-09-29 |
| GB2305921B (en) | 1999-10-20 |
| EP0853661A1 (en) | 1998-07-22 |
| JP4387458B2 (ja) | 2009-12-16 |
| ES2156035T3 (es) | 2001-06-01 |
| JP2000500643A (ja) | 2000-01-25 |
| CA2233042C (en) | 2007-12-18 |
| PT853661E (pt) | 2000-08-31 |
| GB2305921A (en) | 1997-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69611766T2 (de) | Spezifische Bindungspartner für menschliches TGF-beta, Materialien und Verfahren | |
| DE69331903T2 (de) | Veränderte Antikörper, damit zusammenhängende Produkte und Verfahren | |
| AU2020200981B2 (en) | Multispecific antibodies, multispecific activatable antibodies and methods of using the same | |
| DE60012500T2 (de) | Antikörper und antikörperfragmente mit spezifität für tgfbeta1 | |
| DE69934515T2 (de) | Humanisierte monoklonale inetegrin antikörper | |
| DE4193302C2 (de) | Verwendung rekombinanter Antikörper spezifisch für TNF-alpha | |
| DE60116753T2 (de) | Humanisierte antikörper gegen den epidermalen wachstumsfaktorrezeptor | |
| DE69927268T2 (de) | Spezifische antikörper enthaltende bindungsproteine die das nekrotische tumorzentrum binden und deren verwendung | |
| DE60025015T2 (de) | Verfahren zur herstellung von rekombinanten proteinen mittels inhibitoren von apoptose | |
| DE69737683T2 (de) | Antikörper gegen die ed-b domäne von fibronektin, ihre herstellung und verwendungen | |
| RU2360925C2 (ru) | Нейтрализующие антитела против gdf-8 и их применение | |
| DE68913658T3 (de) | Klonierung von Immunglobulin Sequenzen aus den variablen Domänen | |
| JP5583591B2 (ja) | Ｗｉｓｅ結合抗体及びエピトープ | |
| US7368111B2 (en) | Human antibodies specific for TGFβ2 | |
| DE69532889T2 (de) | Interleukin-5-spezifische rekombinante antikörper | |
| JP6430438B2 (ja) | 網膜神経線維層変性の治療に使用するためのｒｇｍ ａタンパク質に対するモノクローナル抗体 | |
| DE69934241T2 (de) | Agonistische antikörper gegen tie2 | |
| KR102866306B1 (ko) | 신경 성장 인자에 대한 단일 클론 항체, 및 이의 코딩 유전자 및 용도 | |
| DE69535319T2 (de) | Rekombinante il-5 antagonisten für die behandlung von il-5 bedingten krankheiten | |
| EP1945767B1 (de) | Identifizierung und charakterisierung von funktionsblockierenden anti-ed-b-fibronektin antikörpern | |
| DE69828154T2 (de) | Anti-alphavbeta3 humanizierte monoklonale antikörper | |
| DE69615843T2 (de) | Il-8 antagonisten zur behandlung von asthma | |
| RU2350623C2 (ru) | АНТИ-Nogo АНТИТЕЛА ("11С7") И ИХ ФАРМАЦЕВТИЧЕСКОЕ ИСПОЛЬЗОВАНИЕ | |
| DE60226253T2 (de) | Humanisierter antikörper gegen fibroblastenwachstumsfaktor 8 und fragment des antikörpers | |
| EA044828B1 (ru) | Моноклональное антитело против фактора роста нервов, кодирующий его ген и его применение |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |