DE69927147T2 - Verwendung von osteoprotegerin zur vorbeugung und behandlung cardiovaskulärer erkrankungen - Google Patents
Verwendung von osteoprotegerin zur vorbeugung und behandlung cardiovaskulärer erkrankungen Download PDFInfo
- Publication number
- DE69927147T2 DE69927147T2 DE69927147T DE69927147T DE69927147T2 DE 69927147 T2 DE69927147 T2 DE 69927147T2 DE 69927147 T DE69927147 T DE 69927147T DE 69927147 T DE69927147 T DE 69927147T DE 69927147 T2 DE69927147 T2 DE 69927147T2
- Authority
- DE
- Germany
- Prior art keywords
- opg
- use according
- osteoprotegerin
- terminus
- polypeptide
- 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
- 108010035042 Osteoprotegerin Proteins 0.000 title claims abstract description 194
- 102000008108 Osteoprotegerin Human genes 0.000 title claims abstract description 193
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 title claims abstract description 190
- 238000011282 treatment Methods 0.000 title claims abstract description 15
- 208000024172 Cardiovascular disease Diseases 0.000 title claims abstract description 11
- 230000002265 prevention Effects 0.000 title claims abstract description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 53
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 49
- 229920001184 polypeptide Polymers 0.000 claims description 48
- 150000007523 nucleic acids Chemical class 0.000 claims description 31
- 108020004707 nucleic acids Proteins 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 24
- 150000001413 amino acids Chemical class 0.000 claims description 23
- 210000004899 c-terminal region Anatomy 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 10
- -1 Vitamin D compounds Chemical class 0.000 claims description 6
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 5
- 230000000123 anti-resoprtive effect Effects 0.000 claims description 4
- 229940011871 estrogen Drugs 0.000 claims description 4
- 239000000262 estrogen Substances 0.000 claims description 4
- 229940095743 selective estrogen receptor modulator Drugs 0.000 claims description 3
- 239000000333 selective estrogen receptor modulator Substances 0.000 claims description 3
- 229930003316 Vitamin D Natural products 0.000 claims description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 2
- 235000019166 vitamin D Nutrition 0.000 claims description 2
- 239000011710 vitamin D Substances 0.000 claims description 2
- 229940046008 vitamin d Drugs 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000011260 co-administration Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 27
- 238000000034 method Methods 0.000 abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 32
- 230000014509 gene expression Effects 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 23
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 23
- 239000013598 vector Substances 0.000 description 18
- 210000000988 bone and bone Anatomy 0.000 description 16
- 229920001223 polyethylene glycol Polymers 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 210000000709 aorta Anatomy 0.000 description 14
- 208000004434 Calcinosis Diseases 0.000 description 13
- 230000002308 calcification Effects 0.000 description 13
- 108020001507 fusion proteins Proteins 0.000 description 13
- 102000037865 fusion proteins Human genes 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 239000000178 monomer Substances 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 230000004071 biological effect Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 208000005475 Vascular calcification Diseases 0.000 description 10
- 210000002254 renal artery Anatomy 0.000 description 10
- 235000018417 cysteine Nutrition 0.000 description 9
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 210000002997 osteoclast Anatomy 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 229910052791 calcium Inorganic materials 0.000 description 7
- 239000003431 cross linking reagent Substances 0.000 description 7
- 238000011813 knockout mouse model Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 208000001132 Osteoporosis Diseases 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 230000001588 bifunctional effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000005647 linker group Chemical group 0.000 description 5
- 210000000963 osteoblast Anatomy 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 238000007901 in situ hybridization Methods 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 101000798130 Homo sapiens Tumor necrosis factor receptor superfamily member 11B Proteins 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 229920000954 Polyglycolide Polymers 0.000 description 3
- 238000002399 angioplasty Methods 0.000 description 3
- 210000002805 bone matrix Anatomy 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000010382 chemical cross-linking Methods 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 238000001446 dark-field microscopy Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000004633 polyglycolic acid Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 102220073915 rs144744634 Human genes 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 3
- 206010002329 Aneurysm Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108060003393 Granulin Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- VYLDEYYOISNGST-UHFFFAOYSA-N bissulfosuccinimidyl suberate Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)C(S(O)(=O)=O)CC1=O VYLDEYYOISNGST-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 102220359469 c.76C>G Human genes 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000000837 carbohydrate group Chemical group 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229920006237 degradable polymer Polymers 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 102000052781 human TNFRSF11B Human genes 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000006320 pegylation Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- CXCHEKCRJQRVNG-UHFFFAOYSA-N 2,2,2-trifluoroethanesulfonyl chloride Chemical compound FC(F)(F)CS(Cl)(=O)=O CXCHEKCRJQRVNG-UHFFFAOYSA-N 0.000 description 1
- 108091005508 Acid proteases Proteins 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 101100338278 Caenorhabditis elegans his-66 gene Proteins 0.000 description 1
- 101100069896 Caenorhabditis elegans his-68 gene Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000055008 Matrilin Proteins Human genes 0.000 description 1
- 108010072582 Matrilin Proteins Proteins 0.000 description 1
- IMTUWVJPCQPJEE-IUCAKERBSA-N Met-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN IMTUWVJPCQPJEE-IUCAKERBSA-N 0.000 description 1
- 208000005447 Monckeberg Medial Calcific Sclerosis Diseases 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 102000009890 Osteonectin Human genes 0.000 description 1
- 108010077077 Osteonectin Proteins 0.000 description 1
- 108091006006 PEGylated Proteins Proteins 0.000 description 1
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102100032236 Tumor necrosis factor receptor superfamily member 11B Human genes 0.000 description 1
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000002617 bone density conservation agent Substances 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910001576 calcium mineral Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940096422 collagen type i Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000035194 endochondral ossification Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 229940085363 evista Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000008069 intimal proliferation Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000021190 leftovers Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 102000043253 matrix Gla protein Human genes 0.000 description 1
- 108010057546 matrix Gla protein Proteins 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- DWCZIOOZPIDHAB-UHFFFAOYSA-L methyl green Chemical group [Cl-].[Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)[N+](C)(C)C)=C1C=CC(=[N+](C)C)C=C1 DWCZIOOZPIDHAB-UHFFFAOYSA-L 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 208000002865 osteopetrosis Diseases 0.000 description 1
- 210000004663 osteoprogenitor cell Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960003330 pentetic acid Drugs 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 229920003192 poly(bis maleimide) Polymers 0.000 description 1
- 229920002401 polyacrylamide Chemical class 0.000 description 1
- 229920000867 polyelectrolyte Chemical class 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000013636 protein dimer Substances 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000003751 purification from natural source Methods 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000001993 wax Substances 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
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64832 | 1998-04-23 | ||
| US09/064,832 US6790823B1 (en) | 1998-04-23 | 1998-04-23 | Compositions and methods for the prevention and treatment of cardiovascular diseases |
| PCT/US1999/008793 WO1999053942A1 (en) | 1998-04-23 | 1999-04-21 | Compositions comprising osteoprotegerin for the prevention and treatment of cardiovascular diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69927147D1 DE69927147D1 (de) | 2005-10-13 |
| DE69927147T2 true DE69927147T2 (de) | 2006-01-26 |
Family
ID=22058524
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69927147T Expired - Lifetime DE69927147T2 (de) | 1998-04-23 | 1999-04-21 | Verwendung von osteoprotegerin zur vorbeugung und behandlung cardiovaskulärer erkrankungen |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6790823B1 (enExample) |
| EP (1) | EP1073456B1 (enExample) |
| JP (1) | JP4776774B2 (enExample) |
| AT (1) | ATE303817T1 (enExample) |
| AU (1) | AU757806B2 (enExample) |
| CA (1) | CA2325360C (enExample) |
| DE (1) | DE69927147T2 (enExample) |
| DK (1) | DK1073456T3 (enExample) |
| ES (1) | ES2248998T3 (enExample) |
| SI (1) | SI1073456T1 (enExample) |
| WO (1) | WO1999053942A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL117175A (en) | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
| 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 |
| US6878811B1 (en) * | 1998-04-23 | 2005-04-12 | Ajinomoto Co., Inc. | Substance with antithrombotic activity and method for detecting glycokallidin |
| ATE412746T1 (de) | 1998-05-14 | 2008-11-15 | Immunex Corp | Verfahren zur hemmung der wirkung der osteoklasten |
| RU2324705C2 (ru) * | 2001-04-03 | 2008-05-20 | Сосьете Де Продюи Нестле С.А. | Остеопротегерин, применение его для изготовления фармацевтической композиции (варианты) и получения пищевого продукта (варианты) и корма для животных, пищевой продукт, корм для животных и фармацевтическая композиция для профилактики или лечения расстройств, связанных с костным ремоделированием, и/или иммунных расстройств |
| US7198798B2 (en) * | 2001-05-10 | 2007-04-03 | University Of Washington | Methods and devices for promoting endothelial morphogenesis |
| DK1572874T3 (da) | 2001-05-25 | 2013-12-16 | Human Genome Sciences Inc | Antistoffer, der immunospecifikt binder til TRAIL receptorer |
| US8649843B2 (en) * | 2001-11-24 | 2014-02-11 | Ben A. Arnold | Automated calcium scoring of the aorta |
| US7718776B2 (en) | 2002-04-05 | 2010-05-18 | Amgen Inc. | Human anti-OPGL neutralizing antibodies as selective OPGL pathway inhibitors |
| US7585840B2 (en) | 2002-04-10 | 2009-09-08 | Merck Serono S.A. | Use of osteoprotegerin for the treatment and/or prevention of fibrotic disease |
| CN1658895A (zh) * | 2002-04-10 | 2005-08-24 | 应用研究系统Ars股份公司 | 护骨素在治疗和／或预防纤维变性疾病中的应用 |
| WO2006047419A2 (en) | 2004-10-25 | 2006-05-04 | Intezyne Technologies, Incorporated | Heterobifunctional poly(ethylene glycol) and uses thereof |
| WO2006074202A2 (en) | 2005-01-04 | 2006-07-13 | Intezyne Technologies, Incorporated | Synthesis of hybrid block copolymers and uses thereof |
| US7561727B2 (en) * | 2005-06-02 | 2009-07-14 | Nordic Bioscience Imaging A/S | Method of deriving a quantitative measure of a degree of calcification of an aorta |
| US7463758B2 (en) * | 2005-06-02 | 2008-12-09 | Nordio Bioscience A/S | Method of deriving a quantitative measure of a degree of calcification of an aorta |
| EP2433644A1 (en) * | 2010-09-22 | 2012-03-28 | IMBA-Institut für Molekulare Biotechnologie GmbH | Breast cancer therapeutics |
| FR2970870A1 (fr) * | 2011-01-31 | 2012-08-03 | Centre Nat Rech Scient | Modulation de la proliferation des cellules epitheliales de l'unite epidermo-pilo-sebacee via rank |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| JP2877509B2 (ja) | 1989-05-19 | 1999-03-31 | アムジエン・インコーポレーテツド | メタロプロテイナーゼ阻害剤 |
| US5580722A (en) * | 1989-07-18 | 1996-12-03 | Oncogene Science, Inc. | Methods of determining chemicals that modulate transcriptionally expression of genes associated with cardiovascular disease |
| US6369027B1 (en) | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
-
1998
- 1998-04-23 US US09/064,832 patent/US6790823B1/en not_active Expired - Fee Related
-
1999
- 1999-04-21 CA CA002325360A patent/CA2325360C/en not_active Expired - Fee Related
- 1999-04-21 WO PCT/US1999/008793 patent/WO1999053942A1/en not_active Ceased
- 1999-04-21 DK DK99918766T patent/DK1073456T3/da active
- 1999-04-21 JP JP2000544345A patent/JP4776774B2/ja not_active Expired - Fee Related
- 1999-04-21 AT AT99918766T patent/ATE303817T1/de active
- 1999-04-21 AU AU36605/99A patent/AU757806B2/en not_active Ceased
- 1999-04-21 ES ES99918766T patent/ES2248998T3/es not_active Expired - Lifetime
- 1999-04-21 DE DE69927147T patent/DE69927147T2/de not_active Expired - Lifetime
- 1999-04-21 EP EP99918766A patent/EP1073456B1/en not_active Expired - Lifetime
- 1999-04-21 SI SI9930826T patent/SI1073456T1/sl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2248998T3 (es) | 2006-03-16 |
| WO1999053942A8 (en) | 1999-12-02 |
| JP4776774B2 (ja) | 2011-09-21 |
| US6790823B1 (en) | 2004-09-14 |
| CA2325360A1 (en) | 1999-10-28 |
| AU757806B2 (en) | 2003-03-06 |
| ATE303817T1 (de) | 2005-09-15 |
| AU3660599A (en) | 1999-11-08 |
| EP1073456A1 (en) | 2001-02-07 |
| SI1073456T1 (sl) | 2005-12-31 |
| DK1073456T3 (da) | 2005-10-24 |
| DE69927147D1 (de) | 2005-10-13 |
| CA2325360C (en) | 2008-11-04 |
| EP1073456B1 (en) | 2005-09-07 |
| JP2002512199A (ja) | 2002-04-23 |
| WO1999053942A1 (en) | 1999-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69927147T2 (de) | Verwendung von osteoprotegerin zur vorbeugung und behandlung cardiovaskulärer erkrankungen | |
| DE69737266T2 (de) | Ob-fusionsprotein enthaltende zusammensetzungen und verfahren | |
| DE69724451T2 (de) | Kombinationtherapie mit einem tnf-bindendem protein zür behandlung von durch tnf verursachten erkrangungen | |
| JP4657388B2 (ja) | オステオプロテゲリン | |
| DE69731834T2 (de) | Agouti verwandtes gen | |
| DE69837845T3 (de) | Osteoprotegerin bindende proteine und deren rezeptoren | |
| DE69737814T2 (de) | Gekürzte lösliche typ-i-rezeptoren für tumor-nekrose-faktor | |
| DE69934425T2 (de) | Thrombopoietin substitute | |
| DE69631605T2 (de) | Verfahren zur verringerung und zur erhaltung von verringerten blutspiegeln von lipiden mittels zubereitungen von ob-proteinen | |
| DE69936315T2 (de) | Fragmente des wachstumsfaktors für bindegewebe (ctgf) und verfahren und anwendungen davon | |
| DE60222882T2 (de) | Peptide und verwandte moleküle, die an tall-1 binden | |
| DE69631544T2 (de) | Fettleibigkeitsprotein (ob) zur erhögung der mageren körpermasse | |
| DE69926536T2 (de) | Antagonisten von vaskular-endothelialen zellwachstumsfaktoren und ihre anwendung | |
| EP1385966A2 (de) | Rekombinante fusionsproteine und deren trimere | |
| DE69924009T2 (de) | Methode zur verstärkung der biologischen aktivität von liganden | |
| US20050221331A1 (en) | Osteoprotegerin | |
| DE69734096T2 (de) | Rezeptor des ob-proteins und verwandte zusammensetzungen und verfahren | |
| DE69912743T2 (de) | Behandlung von follikulären lymphomen unter verwendung von inhibitoren des lymphotoxin (lt)-aktivierungsweges | |
| DE69727691T2 (de) | Verwendung von keratinocyten-wachstumsfaktor-2 | |
| DE60125959T2 (de) | Unterscheidung zwischen gnrh-i und gnrh-ii | |
| MXPA00010113A (en) | Compositions and methods for the prevention and treatment of cardiovascular diseases | |
| TWI221482B (en) | Osteoprotegerin | |
| HK1001526B (en) | Osteoprotegerin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |