ES2317694T3 - Metodo para inhibir la actividad osteoclastica. - Google Patents
Metodo para inhibir la actividad osteoclastica. Download PDFInfo
- Publication number
- ES2317694T3 ES2317694T3 ES99923021T ES99923021T ES2317694T3 ES 2317694 T3 ES2317694 T3 ES 2317694T3 ES 99923021 T ES99923021 T ES 99923021T ES 99923021 T ES99923021 T ES 99923021T ES 2317694 T3 ES2317694 T3 ES 2317694T3
- Authority
- ES
- Spain
- Prior art keywords
- rank
- baselineskip
- amino acid
- protein
- soluble
- 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
- 238000000034 method Methods 0.000 title description 19
- 230000001599 osteoclastic effect Effects 0.000 title description 9
- 102000014128 RANK Ligand Human genes 0.000 claims description 51
- 108010025832 RANK Ligand Proteins 0.000 claims description 51
- 210000002997 osteoclast Anatomy 0.000 claims description 45
- 102000004169 proteins and genes Human genes 0.000 claims description 40
- 108090000623 proteins and genes Proteins 0.000 claims description 40
- 150000001413 amino acids Chemical group 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 25
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 18
- 239000012634 fragment Substances 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 11
- 229920001184 polypeptide Polymers 0.000 claims description 10
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 9
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 7
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 5
- 108060003951 Immunoglobulin Proteins 0.000 claims description 4
- 102000018358 immunoglobulin Human genes 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 108020004414 DNA Proteins 0.000 abstract description 4
- 206010065687 Bone loss Diseases 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 28
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 24
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 24
- 239000003446 ligand Substances 0.000 description 15
- 208000037147 Hypercalcaemia Diseases 0.000 description 12
- 102000008108 Osteoprotegerin Human genes 0.000 description 12
- 108010035042 Osteoprotegerin Proteins 0.000 description 12
- 230000000148 hypercalcaemia Effects 0.000 description 12
- 208000030915 hypercalcemia disease Diseases 0.000 description 12
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 11
- 230000004069 differentiation Effects 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 102000010498 Receptor Activator of Nuclear Factor-kappa B Human genes 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 210000000988 bone and bone Anatomy 0.000 description 8
- 241001529936 Murinae Species 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 208000006386 Bone Resorption Diseases 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000024279 bone resorption Effects 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 6
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000000963 osteoblast Anatomy 0.000 description 5
- 101150013553 CD40 gene Proteins 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 210000002536 stromal cell Anatomy 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 101100044298 Drosophila melanogaster fand gene Proteins 0.000 description 3
- 101150064015 FAS gene Proteins 0.000 description 3
- 241000237955 Nassarius Species 0.000 description 3
- 101100335198 Pneumocystis carinii fol1 gene Proteins 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- -1 diethylaminoethyl groups Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000003606 oligomerizing effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 102000055006 Calcitonin Human genes 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 2
- 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 2
- 108091006020 Fc-tagged proteins Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
- 229960004015 calcitonin Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010001789 Calcitonin Receptors Proteins 0.000 description 1
- 102100038520 Calcitonin receptor Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000648503 Homo sapiens Tumor necrosis factor receptor superfamily member 11A Proteins 0.000 description 1
- 101000798130 Homo sapiens Tumor necrosis factor receptor superfamily member 11B Proteins 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 1
- 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000053530 human TNFRSF11A Human genes 0.000 description 1
- 102000052781 human TNFRSF11B Human genes 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000005088 multinucleated cell Anatomy 0.000 description 1
- 210000001721 multinucleated osteoclast Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 230000002177 osteoclastogenic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 108091006084 receptor activators Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/73—Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/866—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Compounds Of Unknown Constitution (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8548798P | 1998-05-14 | 1998-05-14 | |
| US85487P | 1998-05-14 | ||
| US11083698P | 1998-12-03 | 1998-12-03 | |
| US110836P | 1998-12-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2317694T3 true ES2317694T3 (es) | 2009-04-16 |
Family
ID=26772773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99923021T Expired - Lifetime ES2317694T3 (es) | 1998-05-14 | 1999-05-13 | Metodo para inhibir la actividad osteoclastica. |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US20050089522A1 (enExample) |
| EP (2) | EP1076699B1 (enExample) |
| JP (1) | JP2002514418A (enExample) |
| AT (2) | ATE412746T1 (enExample) |
| AU (1) | AU762574B2 (enExample) |
| CA (1) | CA2328140C (enExample) |
| CY (1) | CY1111912T1 (enExample) |
| DE (1) | DE69939822D1 (enExample) |
| DK (1) | DK2009025T3 (enExample) |
| ES (1) | ES2317694T3 (enExample) |
| PT (1) | PT2009025E (enExample) |
| WO (1) | WO1999058674A2 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL117175A (en) | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
| DE69738811D1 (de) * | 1996-12-13 | 2008-08-14 | Schering Corp | Oberflächenantigene aus Säugern |
| WO1998028424A2 (en) | 1996-12-23 | 1998-07-02 | Immunex Corporation | Receptor activator of nf-kappa b, receptor is member of tnf receptor superfamily |
| NZ332995A (en) | 1997-04-15 | 2000-07-28 | Snow Brand Milk Products Co Ltd | A protein which binds to osteoclastogenesis inhibitory factor (OCIF) |
| US6316408B1 (en) * | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
| BR9808545A (pt) * | 1997-04-16 | 2000-05-23 | Amgen Inc | ácido nucleico isolado, vetor de expressão, célula hospedeira, processos para produzir uma proteìna de ligação da osteoprotegerina, para detectar a presença de uma proteìna de ligação à osteoprotegerina em uma amostra biológica, para avaliar a capacidade de um composto candidato de ligar-se a uma proteìna de ligação da osteoprotegerina e de um composto de teste para aumentar ou reduzir a ligação da proteìna de ligação da osteoprotegerina a odar, para regular a expressão de uma proteìna de ligação da osteoprotegerina em um animal e para prevenir ou tratar de doença óssea em um mamìfero, polipeptìdeo, protéina de ligação da osteroprotegerina purificada e isolada, ou seu fragmento, análogo ou derivado, e, anticorpo ou seu fragmento |
| AU7705098A (en) * | 1997-05-29 | 1998-12-30 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like protein 8 |
| US6891082B2 (en) * | 1997-08-01 | 2005-05-10 | The Johns Hopkins University School Of Medicine | Transgenic non-human animals expressing a truncated activintype II receptor |
| ATE412746T1 (de) | 1998-05-14 | 2008-11-15 | Immunex Corp | Verfahren zur hemmung der wirkung der osteoklasten |
| US6492333B1 (en) | 1999-04-09 | 2002-12-10 | Osteoscreen, Inc. | Treatment of myeloma bone disease with proteasomal and NF-κB activity inhibitors |
| US6673771B1 (en) | 1999-07-28 | 2004-01-06 | The Trustees Of The University Of Pennsylvania | Methods of inhibiting osteoclast activity |
| EP1207873B1 (en) * | 1999-07-28 | 2009-11-18 | The Trustees Of The University Of Pennsylvania | Methods of inhibiting osteoclast activity |
| US20030103978A1 (en) * | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
| EP1399555A2 (en) * | 2001-02-09 | 2004-03-24 | Maxygen Holdings Ltd. c/o Close Brothers (Cayman) Limited | Rank ligand-binding polypeptides |
| EP1385532A4 (en) * | 2001-03-22 | 2004-12-15 | Barnes Jewish Hospital | STIMULATION OF THE OSTEOGENESIS WITH RANG-LIGAND FUSION PROTEINS |
| EP1385872A4 (en) * | 2001-05-11 | 2004-12-15 | Res Dev Foundation | NF-KAPPA B ACTIVATOR RECEPTOR INHIBITORS AND USES OF SUCH INHIBITORS |
| ES2212930T1 (es) * | 2001-05-17 | 2004-08-16 | Immunex Corporation | Uso terapeutico de antagonistas de rank. |
| ES2706902T3 (es) | 2001-06-26 | 2019-04-01 | Amgen Inc | Anticuerpos para OPGL |
| CA2463478A1 (en) * | 2001-10-12 | 2003-08-14 | Barnes-Jewish Hospital | Methods for screening osteogenic compounds |
| US7718776B2 (en) * | 2002-04-05 | 2010-05-18 | Amgen Inc. | Human anti-OPGL neutralizing antibodies as selective OPGL pathway inhibitors |
| AU2003242265A1 (en) * | 2002-06-07 | 2003-12-22 | Sankyo Company, Limited | Combined effects of therapeutic or preventive agent composition for bone breakage |
| TWI359026B (en) * | 2004-02-12 | 2012-03-01 | Sankyo Co | Pharmaceutical composition for the osteoclast rela |
| JP5191487B2 (ja) * | 2007-06-05 | 2013-05-08 | オリエンタル酵母工業株式会社 | 新しい骨量増加薬 |
| JP6403999B2 (ja) * | 2014-06-05 | 2018-10-10 | 株式会社細川洋行 | レトルト包装用積層体及び容器 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6410516B1 (en) * | 1986-01-09 | 2002-06-25 | President & Fellows Of Harvard College | Nuclear factors associated with transcriptional regulation |
| US5716805A (en) | 1991-10-25 | 1998-02-10 | Immunex Corporation | Methods of preparing soluble, oligomeric proteins |
| CA2121798C (en) | 1991-10-25 | 2007-07-24 | Richard J. Armitage | Novel cytokine |
| JP3589665B2 (ja) * | 1992-10-23 | 2004-11-17 | イミュネックス・コーポレーション | 可溶性オリゴマー蛋白質の調製法 |
| US5741667A (en) | 1994-05-27 | 1998-04-21 | Genentech, Inc. | Tumor necrosis factor receptor-associated factors |
| IL117175A (en) | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
| JPH11507205A (ja) | 1995-04-27 | 1999-06-29 | ヒューマン・ジェノム・サイエンシズ・インコーポレイテッド | ヒト腫瘍壊死因子受容体 |
| CA2222914C (en) * | 1995-06-07 | 2002-04-02 | Immunex Corporation | Novel cd40l mutein |
| US6613544B1 (en) | 1995-12-22 | 2003-09-02 | Amgen Inc. | Osteoprotegerin |
| US6369027B1 (en) | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
| JPH1057071A (ja) | 1996-08-19 | 1998-03-03 | Snow Brand Milk Prod Co Ltd | 新規dna及びそれを用いた蛋白質の製造方法 |
| DE69738811D1 (de) | 1996-12-13 | 2008-08-14 | Schering Corp | Oberflächenantigene aus Säugern |
| WO1998028423A2 (en) | 1996-12-20 | 1998-07-02 | Board Of Regents, The University Of Texas System | Compositions and methods of use for osteoclast inhibitory factors |
| WO1998028424A2 (en) * | 1996-12-23 | 1998-07-02 | Immunex Corporation | Receptor activator of nf-kappa b, receptor is member of tnf receptor superfamily |
| US6271349B1 (en) * | 1996-12-23 | 2001-08-07 | Immunex Corporation | Receptor activator of NF-κB |
| NZ332995A (en) * | 1997-04-15 | 2000-07-28 | Snow Brand Milk Products Co Ltd | A protein which binds to osteoclastogenesis inhibitory factor (OCIF) |
| BR9808545A (pt) * | 1997-04-16 | 2000-05-23 | Amgen Inc | ácido nucleico isolado, vetor de expressão, célula hospedeira, processos para produzir uma proteìna de ligação da osteoprotegerina, para detectar a presença de uma proteìna de ligação à osteoprotegerina em uma amostra biológica, para avaliar a capacidade de um composto candidato de ligar-se a uma proteìna de ligação da osteoprotegerina e de um composto de teste para aumentar ou reduzir a ligação da proteìna de ligação da osteoprotegerina a odar, para regular a expressão de uma proteìna de ligação da osteoprotegerina em um animal e para prevenir ou tratar de doença óssea em um mamìfero, polipeptìdeo, protéina de ligação da osteroprotegerina purificada e isolada, ou seu fragmento, análogo ou derivado, e, anticorpo ou seu fragmento |
| US5843678A (en) * | 1997-04-16 | 1998-12-01 | Amgen Inc. | Osteoprotegerin binding proteins |
| US6316408B1 (en) | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
| CA2229449A1 (en) | 1997-04-25 | 1998-10-25 | Takeda Chemical Industries, Ltd. | Novel receptor protein and its use |
| CA2288351A1 (en) | 1997-05-01 | 1998-11-05 | Amgen Inc. | Chimeric opg polypeptides |
| AU7705098A (en) | 1997-05-29 | 1998-12-30 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like protein 8 |
| US6087555A (en) | 1997-10-15 | 2000-07-11 | Amgen Inc. | Mice lacking expression of osteoprotegerin |
| WO1999029865A2 (en) | 1997-12-12 | 1999-06-17 | The Rockefeller University | A protein belonging to the tnf superfamily, nucleic acids encoding same, and methods of use thereof |
| JPH11266872A (ja) | 1998-03-20 | 1999-10-05 | Suntory Ltd | NF−κBの活性化を抑制する物質のスクリーニング方法 |
| US6790823B1 (en) | 1998-04-23 | 2004-09-14 | Amgen Inc. | Compositions and methods for the prevention and treatment of cardiovascular diseases |
| ATE412746T1 (de) | 1998-05-14 | 2008-11-15 | Immunex Corp | Verfahren zur hemmung der wirkung der osteoklasten |
| HUP0102782A3 (en) | 1998-06-19 | 2002-12-28 | Smithkline Beecham Corp | Salycilanilide as inhibitors of transcription factor nf-kb |
| HUP0102492A2 (hu) | 1998-06-19 | 2001-11-28 | Smithkline Beecham Corp. | Amino-indanon származékok alkalmazása NF-kB transzkripciós faktor inhibitor hatású gyógyszerkészítmények előállítására |
| WO2001003719A2 (en) | 1999-07-09 | 2001-01-18 | Amgen Inc. | Combination therapy for conditions leading to bone loss |
| AU6788900A (en) | 1999-09-03 | 2001-04-10 | Amgen, Inc. | Compositions and methods for the prevention or treatment of cancer and bone loss associated with cancer |
| US20030144187A1 (en) | 1999-09-03 | 2003-07-31 | Colin R. Dunstan | Opg fusion protein compositions and methods |
| AUPQ314799A0 (en) | 1999-09-29 | 1999-10-21 | University Of Western Australia, The | Bone cell factor |
| US20030103978A1 (en) | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
| WO2001062932A1 (en) | 2000-02-23 | 2001-08-30 | Amgen Inc. | Antagonistic selective binding agents of osteoprotegerin binding protein |
| WO2002015846A2 (en) | 2000-08-21 | 2002-02-28 | Smithkline Beecham Corporation | Anti-rank ligand monoclonal antibodies useful in treatment of rank ligand mediated disorders |
| ES2706902T3 (es) | 2001-06-26 | 2019-04-01 | Amgen Inc | Anticuerpos para OPGL |
| US7718776B2 (en) | 2002-04-05 | 2010-05-18 | Amgen Inc. | Human anti-OPGL neutralizing antibodies as selective OPGL pathway inhibitors |
-
1999
- 1999-05-13 AT AT99923021T patent/ATE412746T1/de not_active IP Right Cessation
- 1999-05-13 AU AU39888/99A patent/AU762574B2/en not_active Expired
- 1999-05-13 JP JP2000548465A patent/JP2002514418A/ja active Pending
- 1999-05-13 ES ES99923021T patent/ES2317694T3/es not_active Expired - Lifetime
- 1999-05-13 AT AT08015570T patent/ATE517916T1/de active
- 1999-05-13 CA CA2328140A patent/CA2328140C/en not_active Expired - Lifetime
- 1999-05-13 DK DK08015570.8T patent/DK2009025T3/da active
- 1999-05-13 EP EP99923021A patent/EP1076699B1/en not_active Expired - Lifetime
- 1999-05-13 DE DE69939822T patent/DE69939822D1/de not_active Expired - Lifetime
- 1999-05-13 EP EP08015570A patent/EP2009025B1/en not_active Expired - Lifetime
- 1999-05-13 PT PT08015570T patent/PT2009025E/pt unknown
- 1999-05-13 WO PCT/US1999/010588 patent/WO1999058674A2/en not_active Ceased
-
2004
- 2004-11-30 US US10/999,523 patent/US20050089522A1/en not_active Abandoned
-
2008
- 2008-06-11 US US12/137,397 patent/US7790684B2/en not_active Expired - Fee Related
-
2011
- 2011-10-06 CY CY20111100954T patent/CY1111912T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT2009025E (pt) | 2011-09-19 |
| JP2002514418A (ja) | 2002-05-21 |
| CA2328140C (en) | 2012-03-13 |
| US20090004196A1 (en) | 2009-01-01 |
| CY1111912T1 (el) | 2015-11-04 |
| EP1076699A2 (en) | 2001-02-21 |
| DK2009025T3 (da) | 2011-11-14 |
| US20050089522A1 (en) | 2005-04-28 |
| EP2009025B1 (en) | 2011-07-27 |
| ATE517916T1 (de) | 2011-08-15 |
| WO1999058674A2 (en) | 1999-11-18 |
| US7790684B2 (en) | 2010-09-07 |
| AU3988899A (en) | 1999-11-29 |
| ATE412746T1 (de) | 2008-11-15 |
| AU762574B2 (en) | 2003-06-26 |
| EP1076699B1 (en) | 2008-10-29 |
| WO1999058674A3 (en) | 2000-02-10 |
| EP2009025A1 (en) | 2008-12-31 |
| DE69939822D1 (de) | 2008-12-11 |
| CA2328140A1 (en) | 1999-11-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2317694T3 (es) | Metodo para inhibir la actividad osteoclastica. | |
| US8333963B2 (en) | Method of inhibiting osteoclast activity | |
| ES2253753T3 (es) | Citocina que induce apoptosis. | |
| CN114466657B (zh) | 包括蛋白酶激活治疗剂的组合物和方法 | |
| US5674492A (en) | Method of preventing or treating disease characterized by neoplastic cells expressing CD40 | |
| ES2229264T3 (es) | Receptor il-17. | |
| ES2292242T3 (es) | Utilizaciones terapeuticas de polipeptidos homologos de il-17. | |
| CN101484472B (zh) | 改善的sgp130Fc二聚体 | |
| JPH07501698A (ja) | 二価特異性ヘテロ二量体 | |
| AU756759B2 (en) | Protein that binds trail | |
| EP1148065B1 (en) | Fusion proteins comprising two soluble gp130 molecules | |
| TW570801B (en) | Osteoclastgenic inhibitory agent | |
| WO1999003992A1 (en) | Trail receptor | |
| Ashkenazi et al. | Immunoadhesins: an alternative to human monoclonal antibodies | |
| Hwang et al. | A 20 amino acid synthetic peptide of a region from the 55 kDa human TNF receptor inhibits cytolytic and binding activities of recombinant human tumour necrosis factor in vitro | |
| US20130101585A1 (en) | Method of inhibiting osteoclast activity | |
| ES2368101T3 (es) | Procedimiento para inhibición de la actividad de los osteoclastos. | |
| US20220056102A1 (en) | Multi-functional fusion proteins and uses thereof | |
| MXPA97010399A (es) | Citocina que induce apoptosis |