JP6118807B2 - アルカリホスファターゼ及び／又はナトリウム利尿ペプチドを含む組成物、並びにそれを使用する方法 - Google Patents
アルカリホスファターゼ及び／又はナトリウム利尿ペプチドを含む組成物、並びにそれを使用する方法 Download PDFInfo
- Publication number
- JP6118807B2 JP6118807B2 JP2014537254A JP2014537254A JP6118807B2 JP 6118807 B2 JP6118807 B2 JP 6118807B2 JP 2014537254 A JP2014537254 A JP 2014537254A JP 2014537254 A JP2014537254 A JP 2014537254A JP 6118807 B2 JP6118807 B2 JP 6118807B2
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- seq
- sequence
- acid sequence
- 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.)
- Active
Links
- 108020001621 Natriuretic Peptide Proteins 0.000 title claims description 171
- 102000004571 Natriuretic peptide Human genes 0.000 title claims description 171
- 239000000692 natriuretic peptide Substances 0.000 title claims description 137
- 239000000203 mixture Substances 0.000 title claims description 61
- 238000000034 method Methods 0.000 title claims description 52
- 102000002260 Alkaline Phosphatase Human genes 0.000 title claims description 46
- 108020004774 Alkaline Phosphatase Proteins 0.000 title claims description 46
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 383
- 125000000539 amino acid group Chemical group 0.000 claims description 345
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 337
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 314
- 229920001184 polypeptide Polymers 0.000 claims description 306
- 235000001014 amino acid Nutrition 0.000 claims description 222
- 229940024606 amino acid Drugs 0.000 claims description 220
- 150000001413 amino acids Chemical class 0.000 claims description 164
- 210000000988 bone and bone Anatomy 0.000 claims description 111
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 80
- 101000574445 Homo sapiens Alkaline phosphatase, tissue-nonspecific isozyme Proteins 0.000 claims description 78
- 102100025683 Alkaline phosphatase, tissue-nonspecific isozyme Human genes 0.000 claims description 76
- 239000008194 pharmaceutical composition Substances 0.000 claims description 60
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 54
- 108010038664 atrial natriuretic factor receptor B Proteins 0.000 claims description 51
- 230000008685 targeting Effects 0.000 claims description 48
- 210000004899 c-terminal region Anatomy 0.000 claims description 37
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 34
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 26
- 239000012634 fragment Substances 0.000 claims description 25
- 238000003776 cleavage reaction Methods 0.000 claims description 24
- 230000007017 scission Effects 0.000 claims description 24
- 102000005600 Cathepsins Human genes 0.000 claims description 18
- 108010084457 Cathepsins Proteins 0.000 claims description 18
- 235000003704 aspartic acid Nutrition 0.000 claims description 18
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 17
- 229910052720 vanadium Inorganic materials 0.000 claims description 17
- KJBQDYDTQCIAFO-ZLELNMGESA-N (2s)-2-amino-4-methylpentanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(C)C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O KJBQDYDTQCIAFO-ZLELNMGESA-N 0.000 claims description 16
- 208000003019 Neurofibromatosis 1 Diseases 0.000 claims description 15
- 108060003951 Immunoglobulin Proteins 0.000 claims description 14
- 239000000556 agonist Substances 0.000 claims description 14
- 235000013922 glutamic acid Nutrition 0.000 claims description 14
- 239000004220 glutamic acid Substances 0.000 claims description 14
- 102000018358 immunoglobulin Human genes 0.000 claims description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 239000004471 Glycine Substances 0.000 claims description 11
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 claims description 11
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 claims description 11
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 claims description 11
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 claims description 9
- SEFLNGWGXSFZMH-DQZFIDPSSA-N (2s)-2-aminobutanedioic acid;(2s,3s)-2-amino-3-methylpentanoic acid Chemical compound CC[C@H](C)[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC(O)=O SEFLNGWGXSFZMH-DQZFIDPSSA-N 0.000 claims description 8
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 8
- 235000011180 diphosphates Nutrition 0.000 claims description 8
- 102000002451 NPR2 Human genes 0.000 claims 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 286
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 124
- 101800002899 Soluble alkaline phosphatase Proteins 0.000 description 99
- 125000005647 linker group Chemical group 0.000 description 98
- 102000012421 C-Type Natriuretic Peptide Human genes 0.000 description 93
- 101800000060 C-type natriuretic peptide Proteins 0.000 description 93
- 201000010099 disease Diseases 0.000 description 62
- 208000035475 disorder Diseases 0.000 description 62
- 206010058314 Dysplasia Diseases 0.000 description 60
- 230000004927 fusion Effects 0.000 description 60
- 230000035772 mutation Effects 0.000 description 60
- 206010049933 Hypophosphatasia Diseases 0.000 description 57
- 150000007523 nucleic acids Chemical class 0.000 description 57
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 56
- 208000011580 syndromic disease Diseases 0.000 description 52
- 102100039341 Atrial natriuretic peptide receptor 2 Human genes 0.000 description 49
- 108020004707 nucleic acids Proteins 0.000 description 47
- 102000039446 nucleic acids Human genes 0.000 description 47
- 241000699670 Mus sp. Species 0.000 description 44
- 241000282414 Homo sapiens Species 0.000 description 43
- 210000004027 cell Anatomy 0.000 description 39
- -1 Phe Chemical compound 0.000 description 37
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 35
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 33
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 33
- 206010008723 Chondrodystrophy Diseases 0.000 description 31
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 31
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 31
- 208000008919 achondroplasia Diseases 0.000 description 31
- 208000020084 Bone disease Diseases 0.000 description 30
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 29
- 208000009905 Neurofibromatoses Diseases 0.000 description 29
- 230000000694 effects Effects 0.000 description 29
- 201000004931 neurofibromatosis Diseases 0.000 description 29
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 28
- 208000015100 cartilage disease Diseases 0.000 description 28
- 230000005856 abnormality Effects 0.000 description 27
- 210000003414 extremity Anatomy 0.000 description 27
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 27
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 26
- 108090000623 proteins and genes Proteins 0.000 description 26
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 25
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 25
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 25
- 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 25
- 239000013598 vector Substances 0.000 description 23
- 108091035707 Consensus sequence Proteins 0.000 description 22
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 21
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 21
- 210000003625 skull Anatomy 0.000 description 21
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 20
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 20
- 108020001507 fusion proteins Proteins 0.000 description 20
- 102000037865 fusion proteins Human genes 0.000 description 20
- 208000022145 neurocutaneous syndrome Diseases 0.000 description 20
- 230000001717 pathogenic effect Effects 0.000 description 20
- 206010072610 Skeletal dysplasia Diseases 0.000 description 19
- 210000002464 muscle smooth vascular Anatomy 0.000 description 19
- 210000000845 cartilage Anatomy 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 18
- 235000004400 serine Nutrition 0.000 description 18
- 239000011780 sodium chloride Substances 0.000 description 18
- 230000001225 therapeutic effect Effects 0.000 description 18
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 17
- 208000029578 Muscle disease Diseases 0.000 description 17
- 208000021642 Muscular disease Diseases 0.000 description 17
- 108010038640 atrial natriuretic factor receptor A Proteins 0.000 description 17
- 239000003814 drug Substances 0.000 description 17
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 16
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 16
- 206010061728 Bone lesion Diseases 0.000 description 15
- 230000033558 biomineral tissue development Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 15
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 14
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 14
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 14
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 14
- 239000012528 membrane Substances 0.000 description 14
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 13
- 208000020221 Short stature Diseases 0.000 description 13
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 230000012010 growth Effects 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- 206010029748 Noonan syndrome Diseases 0.000 description 12
- 229940088598 enzyme Drugs 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 12
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 12
- 238000004904 shortening Methods 0.000 description 12
- 101001128963 Homo sapiens Protein Dr1 Proteins 0.000 description 11
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 11
- 102100031227 Protein Dr1 Human genes 0.000 description 11
- 230000002411 adverse Effects 0.000 description 11
- 230000018678 bone mineralization Effects 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 238000013270 controlled release Methods 0.000 description 11
- 230000014509 gene expression Effects 0.000 description 11
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 11
- 239000001509 sodium citrate Substances 0.000 description 11
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 11
- 229940038773 trisodium citrate Drugs 0.000 description 11
- 206010061762 Chondropathy Diseases 0.000 description 10
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
- 206010031243 Osteogenesis imperfecta Diseases 0.000 description 10
- 238000007792 addition Methods 0.000 description 10
- 230000008901 benefit Effects 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 10
- 235000018417 cysteine Nutrition 0.000 description 10
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 229910052727 yttrium Inorganic materials 0.000 description 10
- 108010044467 Isoenzymes Proteins 0.000 description 9
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 9
- 102000003729 Neprilysin Human genes 0.000 description 9
- 108090000028 Neprilysin Proteins 0.000 description 9
- 235000004279 alanine Nutrition 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 239000000539 dimer Substances 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 230000009984 peri-natal effect Effects 0.000 description 9
- 229910052698 phosphorus Inorganic materials 0.000 description 9
- 210000002303 tibia Anatomy 0.000 description 9
- 201000010028 Acrocephalosyndactylia Diseases 0.000 description 8
- 206010010356 Congenital anomaly Diseases 0.000 description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 8
- 102000043136 MAP kinase family Human genes 0.000 description 8
- 108091054455 MAP kinase family Proteins 0.000 description 8
- 101100180983 Mus musculus Khdrbs3 gene Proteins 0.000 description 8
- 208000024834 Neurofibromatosis type 1 Diseases 0.000 description 8
- 108010085793 Neurofibromin 1 Proteins 0.000 description 8
- 241001415513 Salpida Species 0.000 description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 8
- 239000004473 Threonine Substances 0.000 description 8
- 230000002159 abnormal effect Effects 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 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 8
- 238000002887 multiple sequence alignment Methods 0.000 description 8
- 208000007442 rickets Diseases 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 239000004474 valine Substances 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 108090000625 Cathepsin K Proteins 0.000 description 7
- 102000004171 Cathepsin K Human genes 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000002308 calcification Effects 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 201000010828 metaphyseal dysplasia Diseases 0.000 description 7
- 210000001872 metatarsal bone Anatomy 0.000 description 7
- 230000037361 pathway Effects 0.000 description 7
- 229910052721 tungsten Inorganic materials 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
- WMSPZRZYIGOEDS-QMMMGPOBSA-N 4-[[(1s)-5-amino-1-carboxypentyl]amino]-3,5-dinitrobenzoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC1=C([N+]([O-])=O)C=C(C(O)=O)C=C1[N+]([O-])=O WMSPZRZYIGOEDS-QMMMGPOBSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 241000282326 Felis catus Species 0.000 description 6
- 102100021496 Insulin-degrading enzyme Human genes 0.000 description 6
- 108090000828 Insulysin Proteins 0.000 description 6
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 101100084030 Mus musculus Alpl gene Proteins 0.000 description 6
- 102100026379 Neurofibromin Human genes 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000008468 bone growth Effects 0.000 description 6
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 6
- 210000001612 chondrocyte Anatomy 0.000 description 6
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 230000007812 deficiency Effects 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 238000001415 gene therapy Methods 0.000 description 6
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 6
- 230000003902 lesion Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 210000000963 osteoblast Anatomy 0.000 description 6
- 210000000614 rib Anatomy 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 5
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 5
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 5
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 5
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 5
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 5
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 5
- 108010016626 Dipeptides Proteins 0.000 description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 5
- 201000004404 Neurofibroma Diseases 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 231100000518 lethal Toxicity 0.000 description 5
- 230000001665 lethal effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 5
- 208000005368 osteomalacia Diseases 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 102000016914 ras Proteins Human genes 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 210000000689 upper leg Anatomy 0.000 description 5
- RGCKGOZRHPZPFP-UHFFFAOYSA-N Alizarin Natural products C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 4
- 102100024321 Alkaline phosphatase, placental type Human genes 0.000 description 4
- 208000025490 Apert syndrome Diseases 0.000 description 4
- 206010003591 Ataxia Diseases 0.000 description 4
- 206010006002 Bone pain Diseases 0.000 description 4
- 241000282465 Canis Species 0.000 description 4
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 4
- 208000032170 Congenital Abnormalities Diseases 0.000 description 4
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 4
- 101000615334 Homo sapiens Antileukoproteinase Proteins 0.000 description 4
- 101000961040 Homo sapiens Atrial natriuretic peptide receptor 2 Proteins 0.000 description 4
- 101000897494 Homo sapiens C-C motif chemokine 27 Proteins 0.000 description 4
- 208000009289 Jackson-Weiss syndrome Diseases 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical group C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 201000004014 Pfeiffer syndrome Diseases 0.000 description 4
- 101710118538 Protease Proteins 0.000 description 4
- 201000001718 Roberts syndrome Diseases 0.000 description 4
- 208000006938 Schwannomatosis Diseases 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 208000014070 Vestibular schwannoma Diseases 0.000 description 4
- 208000004064 acoustic neuroma Diseases 0.000 description 4
- HFVAFDPGUJEFBQ-UHFFFAOYSA-M alizarin red S Chemical compound [Na+].O=C1C2=CC=CC=C2C(=O)C2=C1C=C(S([O-])(=O)=O)C(O)=C2O HFVAFDPGUJEFBQ-UHFFFAOYSA-M 0.000 description 4
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004489 deciduous teeth Anatomy 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 150000002333 glycines Chemical class 0.000 description 4
- 230000000004 hemodynamic effect Effects 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 208000010978 mucopolysaccharidosis type 4 Diseases 0.000 description 4
- 201000009494 neurilemmomatosis Diseases 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 108010031345 placental alkaline phosphatase Proteins 0.000 description 4
- 230000004481 post-translational protein modification Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 238000011287 therapeutic dose Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 206010011878 Deafness Diseases 0.000 description 3
- 206010013883 Dwarfism Diseases 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 206010053759 Growth retardation Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 208000029663 Hypophosphatemia Diseases 0.000 description 3
- 102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 3
- 101710184243 Intestinal-type alkaline phosphatase Proteins 0.000 description 3
- 229940124647 MEK inhibitor Drugs 0.000 description 3
- 208000001826 Marfan syndrome Diseases 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 229920000805 Polyaspartic acid Polymers 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 3
- DVEXZJFMOKTQEZ-JYFOCSDGSA-N U0126 Chemical compound C=1C=CC=C(N)C=1SC(\N)=C(/C#N)\C(\C#N)=C(/N)SC1=CC=CC=C1N DVEXZJFMOKTQEZ-JYFOCSDGSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 235000008206 alpha-amino acids Nutrition 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000002805 bone matrix Anatomy 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 3
- 210000000038 chest Anatomy 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- OLSDWRNWUGHKSY-UHFFFAOYSA-J dicalcium;phosphonato phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O OLSDWRNWUGHKSY-UHFFFAOYSA-J 0.000 description 3
- 238000003182 dose-response assay Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 210000003811 finger Anatomy 0.000 description 3
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 3
- 231100000001 growth retardation Toxicity 0.000 description 3
- 230000010370 hearing loss Effects 0.000 description 3
- 231100000888 hearing loss Toxicity 0.000 description 3
- 208000016354 hearing loss disease Diseases 0.000 description 3
- 208000003906 hydrocephalus Diseases 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 208000011111 hypophosphatemic rickets Diseases 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical group CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 238000002732 pharmacokinetic assay Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 108010064470 polyaspartate Proteins 0.000 description 3
- 208000003580 polydactyly Diseases 0.000 description 3
- 208000001061 polyostotic fibrous dysplasia Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 210000002320 radius Anatomy 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000002864 sequence alignment Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 102100034605 Atrial natriuretic peptide receptor 3 Human genes 0.000 description 2
- 208000000659 Autoimmune lymphoproliferative syndrome Diseases 0.000 description 2
- 208000000412 Avitaminosis Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 2
- 102000008143 Bone Morphogenetic Protein 2 Human genes 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 208000017501 CBL-related disease Diseases 0.000 description 2
- 208000009447 Cardiac Edema Diseases 0.000 description 2
- 206010007556 Cardiac failure acute Diseases 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 206010067380 Costello Syndrome Diseases 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- 208000018035 Dental disease Diseases 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 2
- NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 description 2
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 2
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 2
- 241001317099 Dystaxia Species 0.000 description 2
- 108091008794 FGF receptors Proteins 0.000 description 2
- 208000016264 Femoral agenesis/hypoplasia Diseases 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- 102000018898 GTPase-Activating Proteins Human genes 0.000 description 2
- 108091006094 GTPase-accelerating proteins Proteins 0.000 description 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 101000924488 Homo sapiens Atrial natriuretic peptide receptor 3 Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 208000005101 LEOPARD Syndrome Diseases 0.000 description 2
- 208000006286 Legius syndrome Diseases 0.000 description 2
- 208000006824 Lichtenstein syndrome Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 2
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 2
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 2
- 206010027145 Melanocytic naevus Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000007326 Muenke Syndrome Diseases 0.000 description 2
- 208000003452 Multiple Hereditary Exostoses Diseases 0.000 description 2
- 206010062901 Multiple lentigines syndrome Diseases 0.000 description 2
- 208000010428 Muscle Weakness Diseases 0.000 description 2
- 206010028372 Muscular weakness Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 208000007256 Nevus Diseases 0.000 description 2
- 101150083321 Nf1 gene Proteins 0.000 description 2
- 208000010708 Noonan syndrome with multiple lentigines Diseases 0.000 description 2
- 208000033633 Noonan syndrome-like disorder with juvenile myelomonocytic leukemia Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 208000000035 Osteochondroma Diseases 0.000 description 2
- 201000010452 Osteogenesis imperfecta type 2 Diseases 0.000 description 2
- 108090000526 Papain Proteins 0.000 description 2
- 241000009328 Perro Species 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 108010020346 Polyglutamic Acid Proteins 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 201000002154 Pterygium Diseases 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N Pyridoxal Chemical compound CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 208000033787 Rare developmental defect during embryogenesis Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 208000009163 Sebaceous of Jadassohn Nevus Diseases 0.000 description 2
- 206010043189 Telangiectasia Diseases 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 208000021017 Weight Gain Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 208000012998 acute renal failure Diseases 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- UASRYODFRYWBRC-UHFFFAOYSA-N cGMP Natural products N1C(N)=NC(=O)C2=C1N(C1C3OP(O)(=O)OC3C(CO)O1)C=N2 UASRYODFRYWBRC-UHFFFAOYSA-N 0.000 description 2
- 208000014729 capillary malformation Diseases 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 208000022734 developmental defect during embryogenesis Diseases 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 206010016629 fibroma Diseases 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000007897 gelcap Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 description 2
- 239000001087 glyceryl triacetate Substances 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 208000014617 hemorrhoid Diseases 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 2
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 2
- 201000010118 hypomelanosis of Ito Diseases 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 208000020038 linear nevus sebaceous syndrome Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229910001425 magnesium ion Inorganic materials 0.000 description 2
- 208000035853 malformation syndrome Diseases 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000004579 marble Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000004220 muscle function Effects 0.000 description 2
- 230000002071 myeloproliferative effect Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000001452 natriuretic effect Effects 0.000 description 2
- 239000006225 natural substrate Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 208000024550 neurocutaneous melanocytosis Diseases 0.000 description 2
- 208000024645 nevus of Ito Diseases 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 229940055729 papain Drugs 0.000 description 2
- 235000019834 papain Nutrition 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 208000031223 plasma cell leukemia Diseases 0.000 description 2
- 229920002643 polyglutamic acid Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 235000013930 proline Nutrition 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 108010023714 recombinant human bone morphogenetic protein-2 Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 206010039722 scoliosis Diseases 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 208000005706 short rib-polydactyly syndrome Diseases 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 231100001055 skeletal defect Toxicity 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 208000009056 telangiectasis Diseases 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 229960002622 triacetin Drugs 0.000 description 2
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 2
- 208000009999 tuberous sclerosis Diseases 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000000623 ulna Anatomy 0.000 description 2
- 241000990167 unclassified Simian adenoviruses Species 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- OCUSNPIJIZCRSZ-ZTZWCFDHSA-N (2s)-2-amino-3-methylbutanoic acid;(2s)-2-amino-4-methylpentanoic acid;(2s,3s)-2-amino-3-methylpentanoic acid Chemical group CC(C)[C@H](N)C(O)=O.CC[C@H](C)[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O OCUSNPIJIZCRSZ-ZTZWCFDHSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- PZBLUWVMZMXIKZ-UHFFFAOYSA-N 2-o-(2-ethoxy-2-oxoethyl) 1-o-ethyl benzene-1,2-dicarboxylate Chemical compound CCOC(=O)COC(=O)C1=CC=CC=C1C(=O)OCC PZBLUWVMZMXIKZ-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 102100024522 Bladder cancer-associated protein Human genes 0.000 description 1
- 101150110835 Blcap gene Proteins 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006237 Breast dysplasia Diseases 0.000 description 1
- GOJCZVPJCKEBQV-UHFFFAOYSA-N Butyl phthalyl butylglycolate Chemical compound CCCCOC(=O)COC(=O)C1=CC=CC=C1C(=O)OCCCC GOJCZVPJCKEBQV-UHFFFAOYSA-N 0.000 description 1
- 101100067721 Caenorhabditis elegans gly-3 gene Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 206010007270 Carcinoid syndrome Diseases 0.000 description 1
- 206010007747 Cataract congenital Diseases 0.000 description 1
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- 208000003417 Central Sleep Apnea Diseases 0.000 description 1
- 206010008252 Cervical cord compression Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008690 Chondrocalcinosis pyrophosphate Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009269 Cleft palate Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010062344 Congenital musculoskeletal anomaly Diseases 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 208000013558 Developmental Bone disease Diseases 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 1
- 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010066054 Dysmorphism Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- 101150029662 E1 gene Proteins 0.000 description 1
- 208000031213 Epidermal nevus syndrome Diseases 0.000 description 1
- 208000019028 Epidermal thickening Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 208000035028 Familial calcium pyrophosphate deposition Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 208000000571 Fibrocystic breast disease Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000006334 Gingival Fibromatosis Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000030839 Hereditary gingival fibromatosis Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000749809 Homo sapiens 2',3'-cyclic-nucleotide 3'-phosphodiesterase Proteins 0.000 description 1
- 101500027325 Homo sapiens Atrial natriuretic peptide Proteins 0.000 description 1
- 101000961044 Homo sapiens Atrial natriuretic peptide receptor 1 Proteins 0.000 description 1
- 101500026735 Homo sapiens Brain natriuretic peptide 32 Proteins 0.000 description 1
- 101000796277 Homo sapiens C-type natriuretic peptide Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000780028 Homo sapiens Natriuretic peptides A Proteins 0.000 description 1
- 101500027331 Homo sapiens Urodilatin Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 208000011327 Increased bone mineral density Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical class OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 208000035752 Live birth Diseases 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 101710113100 Membrane-bound alkaline phosphatase Proteins 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 102100034296 Natriuretic peptides A Human genes 0.000 description 1
- 241000475481 Nebula Species 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 101100493740 Oryza sativa subsp. japonica BC10 gene Proteins 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000012641 Pigmentation disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010059011 Rib deformity Diseases 0.000 description 1
- 208000027790 Rib fracture Diseases 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 206010041549 Spinal cord compression Diseases 0.000 description 1
- 208000014151 Stomatognathic disease Diseases 0.000 description 1
- 206010042265 Sturge-Weber Syndrome Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010042778 Syndactyly Diseases 0.000 description 1
- 108010076818 TEV protease Proteins 0.000 description 1
- 208000008312 Tooth Loss Diseases 0.000 description 1
- 241000219793 Trifolium Species 0.000 description 1
- 108010028230 Trp-Ser- His-Pro-Gln-Phe-Glu-Lys Proteins 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010047627 Vitamin deficiencies Diseases 0.000 description 1
- 208000026724 Waardenburg syndrome Diseases 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 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 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 206010002320 anencephaly Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 208000013914 atrial heart septal defect Diseases 0.000 description 1
- 210000002072 atrial myocyte Anatomy 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 208000025261 autosomal dominant disease Diseases 0.000 description 1
- 208000021018 autosomal dominant inheritance Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000005452 bending Methods 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
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000007470 bone biopsy Methods 0.000 description 1
- 201000006715 brachydactyly Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 229910001424 calcium ion 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
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000022159 cartilage development Effects 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000008455 chondrocalcinosis 2 Diseases 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024035 chronic otitis media Diseases 0.000 description 1
- 210000003109 clavicle Anatomy 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000003340 combinatorial analysis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000005115 demineralization Methods 0.000 description 1
- 230000002328 demineralizing effect Effects 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- 210000001750 dental cementum Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940099371 diacetylated monoglycerides Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- PCYQQSKDZQTOQG-NXEZZACHSA-N dibutyl (2r,3r)-2,3-dihydroxybutanedioate Chemical compound CCCCOC(=O)[C@H](O)[C@@H](O)C(=O)OCCCC PCYQQSKDZQTOQG-NXEZZACHSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FBSAITBEAPNWJG-UHFFFAOYSA-N dimethyl phthalate Natural products CC(=O)OC1=CC=CC=C1OC(C)=O FBSAITBEAPNWJG-UHFFFAOYSA-N 0.000 description 1
- 229960001826 dimethylphthalate Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000035194 endochondral ossification Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002641 enzyme replacement therapy Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 231100000040 eye damage Toxicity 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 206010049444 fibromatosis Diseases 0.000 description 1
- 201000010103 fibrous dysplasia Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000004905 finger nail Anatomy 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000004349 growth plate Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 210000000474 heel Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000045328 human ALPL Human genes 0.000 description 1
- 102000047974 human CNP Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000002758 humerus Anatomy 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000037417 hyperactivation Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 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
- 201000006370 kidney failure Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000010603 microCT Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- JSOQIZDOEIKRLY-UHFFFAOYSA-N n-propylnitrous amide Chemical compound CCCNN=O JSOQIZDOEIKRLY-UHFFFAOYSA-N 0.000 description 1
- 102000027424 natriuretic peptide receptors Human genes 0.000 description 1
- 108091008599 natriuretic peptide receptors Proteins 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007433 nerve pathway Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000006943 neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000029278 non-syndromic brachydactyly of fingers Diseases 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 230000001254 nonsecretory effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 208000003278 patent ductus arteriosus Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 210000002379 periodontal ligament Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000002994 phenylalanines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 235000017924 poor diet Nutrition 0.000 description 1
- 230000007542 postnatal development Effects 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 229960003581 pyridoxal Drugs 0.000 description 1
- 235000008164 pyridoxal Nutrition 0.000 description 1
- 239000011674 pyridoxal Substances 0.000 description 1
- 229940079889 pyrrolidonecarboxylic acid Drugs 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000015590 smooth muscle cell migration Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000012237 sodium aluminium phosphate Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000005198 spinal stenosis Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 208000002254 stillbirth Diseases 0.000 description 1
- 231100000537 stillbirth Toxicity 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical class CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000005086 tooth mineralization Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- IQQWMJSNEUUJAY-UHFFFAOYSA-D trialuminum;sodium;dihydrogen phosphate;hydrogen phosphate;tetrahydrate Chemical compound O.O.O.O.[Na+].[Al+3].[Al+3].[Al+3].OP(O)([O-])=O.OP(O)([O-])=O.OP(O)([O-])=O.OP(O)([O-])=O.OP(O)([O-])=O.OP(O)([O-])=O.OP([O-])([O-])=O.OP([O-])([O-])=O IQQWMJSNEUUJAY-UHFFFAOYSA-D 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
- YZWRNSARCRTXDS-UHFFFAOYSA-N tripropionin Chemical compound CCC(=O)OCC(OC(=O)CC)COC(=O)CC YZWRNSARCRTXDS-UHFFFAOYSA-N 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- IUCCYQIEZNQWRS-DWWHXVEHSA-N ularitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 IUCCYQIEZNQWRS-DWWHXVEHSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000005243 upper chamber Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 230000007279 water homeostasis Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Images
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
- C07K14/575—Hormones
- C07K14/58—Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Cardionatrin; Cardiodilatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- A61P13/06—Anti-spasmodics
-
- 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
- A61P19/00—Drugs for skeletal disorders
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Biotechnology (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161549047P | 2011-10-19 | 2011-10-19 | |
| US61/549,047 | 2011-10-19 | ||
| US201261649717P | 2012-05-21 | 2012-05-21 | |
| US61/649,717 | 2012-05-21 | ||
| PCT/US2012/060869 WO2013059491A1 (en) | 2011-10-19 | 2012-10-18 | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015502336A JP2015502336A (ja) | 2015-01-22 |
| JP2015502336A5 JP2015502336A5 (enExample) | 2015-12-03 |
| JP6118807B2 true JP6118807B2 (ja) | 2017-04-19 |
Family
ID=48141235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014537254A Active JP6118807B2 (ja) | 2011-10-19 | 2012-10-18 | アルカリホスファターゼ及び／又はナトリウム利尿ペプチドを含む組成物、並びにそれを使用する方法 |
Country Status (8)
| Country | Link |
|---|---|
| EP (2) | EP3488861B1 (enExample) |
| JP (1) | JP6118807B2 (enExample) |
| KR (1) | KR20140084201A (enExample) |
| CA (1) | CA2852874A1 (enExample) |
| ES (2) | ES2944087T3 (enExample) |
| HK (1) | HK1201446A1 (enExample) |
| SG (1) | SG11201401605QA (enExample) |
| WO (2) | WO2013058833A1 (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2348114T3 (pl) | 2004-04-21 | 2019-08-30 | Alexion Pharmaceuticals, Inc. | Koniugaty do dostarczania do kości i sposób ich wykorzystania do nakierowywania białek na kość |
| EP2658979B1 (en) * | 2010-12-27 | 2018-02-14 | Alexion Pharmaceuticals, Inc. | Compositions comprising natriuretic peptides and methods of use thereof |
| US10052366B2 (en) | 2012-05-21 | 2018-08-21 | Alexion Pharmaceuticsl, Inc. | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof |
| US10822596B2 (en) | 2014-07-11 | 2020-11-03 | Alexion Pharmaceuticals, Inc. | Compositions and methods for treating craniosynostosis |
| WO2016090251A1 (en) | 2014-12-05 | 2016-06-09 | Alexion Pharmaceuticals, Inc. | Treating seizure with recombinant alkaline phosphatase |
| US10603361B2 (en) | 2015-01-28 | 2020-03-31 | Alexion Pharmaceuticals, Inc. | Methods of treating a subject with an alkaline phosphatase deficiency |
| JP6693134B2 (ja) * | 2015-02-02 | 2020-05-13 | 東ソー株式会社 | リンカー配列を有する抗体及びそれを用いた測定法 |
| KR102789821B1 (ko) * | 2015-03-31 | 2025-04-02 | 소리소 파마슈티컬스 인크. | 프로테아제-절단가능 링커를 갖는 펩티드 구조물 |
| JP2018511346A (ja) | 2015-03-31 | 2018-04-26 | ブイエイチスクエアード リミテッド | ポリペプチド |
| MX2017012662A (es) | 2015-03-31 | 2018-05-11 | Vhsquared Ltd | Polipeptidos. |
| CA2994280C (en) | 2015-07-30 | 2024-01-23 | Biomarin Pharmaceutical Inc. | Use of c-type natriuretic peptide variants to treat skeletal dysplasia |
| AU2016308624B2 (en) | 2015-08-17 | 2022-06-23 | Alexion Pharmaceuticals, Inc. | Manufacturing of alkaline phosphatases |
| EP3355904A4 (en) * | 2015-09-28 | 2019-06-12 | Alexion Pharmaceuticals, Inc. | IDENTIFICATION OF EFFECTIVE DOSE SHEETS FOR TISSUE-SPECIFIC ALKALINE PHOSPHATASE ENZYMERSAT THERAPY OF HYPOPHOSPHATASIA |
| JP2018533571A (ja) | 2015-10-30 | 2018-11-15 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 患者の頭蓋縫合早期癒合症を治療するための方法 |
| EP3426286A4 (en) | 2016-03-08 | 2019-12-04 | Alexion Pharmaceuticals, Inc. | PROCESS FOR TREATING HYPOPHOSPHATASIA IN CHILDREN |
| WO2017173395A1 (en) | 2016-04-01 | 2017-10-05 | Alexion Pharmaceuticals, Inc. | Methods for treating hypophosphatasia in adolescents and adults |
| KR20180125979A (ko) * | 2016-04-01 | 2018-11-26 | 알렉시온 파마슈티칼스, 인코포레이티드 | 알칼리성 포스파타아제로 근육 약화의 치료 |
| CN118078956A (zh) * | 2016-05-06 | 2024-05-28 | 免疫新炉有限公司 | 用于受控和持续释放的elp融合蛋白 |
| US10988744B2 (en) | 2016-06-06 | 2021-04-27 | Alexion Pharmaceuticals, Inc. | Method of producing alkaline phosphatase |
| JP7018933B2 (ja) * | 2016-08-18 | 2022-02-14 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 気管気管支軟化症の治療方法 |
| WO2018060453A1 (en) | 2016-09-30 | 2018-04-05 | Vhsquared Limited | Compositions |
| TWI787230B (zh) | 2017-01-20 | 2022-12-21 | 法商賽諾菲公司 | 抗ＴＧＦ-β抗體及其用途 |
| TWI788321B (zh) | 2017-01-20 | 2023-01-01 | 美商健臻公司 | 骨靶向抗體 |
| MX2019011508A (es) | 2017-03-31 | 2019-11-01 | Alexion Pharma Inc | Metodos para tratar la hipofosfatasia (hpp) en adultos y adolescentes. |
| EP3737750B1 (en) | 2018-01-09 | 2024-06-05 | Theriva Biologics, Inc. | Alkaline phosphatase agents for treatment of neurodevelopmental disorders |
| ES3032290T3 (en) | 2018-03-20 | 2025-07-16 | Theriva Biologics Inc | Intestinal alkaline phosphatase formulations |
| WO2019183209A1 (en) | 2018-03-20 | 2019-09-26 | Synthetic Biologics, Inc. | Alkaline phosphatase agents for treatment of radiation disorders |
| US11913039B2 (en) | 2018-03-30 | 2024-02-27 | Alexion Pharmaceuticals, Inc. | Method for producing recombinant alkaline phosphatase |
| JP7820148B2 (ja) | 2018-08-10 | 2026-02-25 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | アルカリホスファターゼを用いて神経線維腫症１型および関連状態を治療する方法 |
| KR20220005560A (ko) | 2019-05-06 | 2022-01-13 | 신세틱 바이오로직스, 인코퍼레이티드 | 알칼리성 포스페이트-기반 종양학 치료제 |
| EP3986570A1 (en) | 2019-06-21 | 2022-04-27 | Sorriso Pharmaceuticals, Inc. | Compositions |
| EP3986571A1 (en) | 2019-06-21 | 2022-04-27 | Sorriso Pharmaceuticals, Inc. | Polypeptides |
| CN114514243B (zh) | 2019-06-21 | 2025-01-24 | 索瑞索制药公司 | 多肽 |
| MX2022007114A (es) * | 2019-12-09 | 2022-07-11 | Alexion Pharma Inc | Polipeptidos de fosfatasa alcalina y metodos de uso de los mismos. |
| CN116848146A (zh) * | 2020-09-03 | 2023-10-03 | I·S·Y·陈 | 可溶性碱性磷酸酶构建体和包含编码可溶性碱性磷酸酶构建体的多核苷酸的表达载体 |
| MX2023002673A (es) | 2020-09-04 | 2023-05-12 | Alexion Pharma Inc | Métodos para el tratamiento de trastornos de mineralización ósea. |
| EP4291224A4 (en) | 2021-02-12 | 2025-01-01 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| CN119256089A (zh) * | 2022-03-11 | 2025-01-03 | 阿维麦克思生物制药公司 | 用于表达治疗剂的组合物和方法 |
| US12077561B2 (en) | 2022-11-02 | 2024-09-03 | Novo Nordisk A/S | CNP compounds |
| CN116286763B (zh) * | 2023-02-28 | 2024-06-25 | 西北工业大学 | 一种热稳定性提高的胱硫醚β-合成酶突变体及应用 |
| AU2024283779A1 (en) * | 2023-06-07 | 2026-01-22 | Biomarin Pharmaceutical Inc. | High throughput screen for genetic variants associated with short stature |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991016342A1 (fr) | 1990-04-20 | 1991-10-31 | Hisayuki Matsuo | Nouveau peptide a activite physiologique d'origine porcine |
| JP2930380B2 (ja) | 1990-07-13 | 1999-08-03 | 壽之 松尾 | ブタ由来新規生理活性ペプチド（ｃｎｐ―５３） |
| JP3026351B2 (ja) | 1990-07-13 | 2000-03-27 | 壽之 松尾 | ブタｃｎｐ遺伝子及び前駆体蛋白 |
| JP3026354B2 (ja) | 1990-09-27 | 2000-03-27 | 壽之 松尾 | ヒトｃｎｐ遺伝子及び前駆体蛋白 |
| US5626863A (en) | 1992-02-28 | 1997-05-06 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
| JP2809533B2 (ja) | 1991-01-31 | 1998-10-08 | 壽之 松尾 | Ｃｎｐ類似体ペプチド |
| AU6360394A (en) | 1993-03-03 | 1994-09-26 | Mayo Foundation For Medical Education And Research | Vasonatrin peptide and analogs thereof |
| WO1998010087A1 (en) | 1996-09-06 | 1998-03-12 | Trustees Of The University Of Pennsylvania | Chimpanzee adenovirus vectors |
| DE60034478T2 (de) | 1999-11-16 | 2008-01-10 | Genzyme Corp., Cambridge | Vektoren und transgene mit regulatorischen elementen zur genverabreichung in leber |
| US6407211B1 (en) | 1999-12-17 | 2002-06-18 | Mayo Foundation For Medical Education And Research | Chimeric natriuretic peptides |
| JP2002178279A (ja) | 2000-12-12 | 2002-06-25 | Ulvac Japan Ltd | 基板搬送方法 |
| IL142118A0 (en) | 2001-03-20 | 2002-03-10 | Prochon Biotech Ltd | Method and composition for treatment of skeletal dysplasias |
| EP1395293B1 (en) | 2001-05-14 | 2009-07-22 | Gbp Ip, Llc | Lentiviral vectors encoding clotting factors for gene therapy |
| BRPI0203172B8 (pt) | 2001-09-28 | 2021-05-25 | Nakao Kazuwa | composição farmacêutica para acondroplasia |
| HU230364B1 (hu) | 2001-11-21 | 2016-03-29 | The Trustees Of The University Of Pennsylvania | Simian adenovírus nukleinsav és aminosav-szekvencia, azt tartalmazó vektorok, és eljárások annak alkalmazására |
| CA2433479A1 (en) | 2002-07-22 | 2004-01-22 | F. Hoffmann-La Roche Ag | Conjugate of a tissue non-specific alkaline phosphatase and dextran, process for its production and use thereof |
| BR0316560A (pt) | 2002-11-26 | 2005-10-04 | Nobex Corp | Conjugado de composto natriurético, formulação farmacêutica, método de tratar uma condição, método de preparação do conjugado de composto natriurético, conjugado de peptìdeo pró-polinatriurético modificado, análogo de peptìdeo natriurético, análogo de hbnp, composto, e, método de preparar um composto |
| JP2007501021A (ja) | 2003-05-30 | 2007-01-25 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 遺伝子操作された定常領域を含む、抗体および融合タンパク質 |
| WO2005094889A1 (ja) | 2004-03-31 | 2005-10-13 | Chugai Seiyaku Kabushiki Kaisha | 関節炎症治療剤又は予防剤 |
| EP3620530A1 (en) | 2004-03-31 | 2020-03-11 | Kazuwa Nakao | Composition for increasing body height |
| JP2005292718A (ja) | 2004-04-05 | 2005-10-20 | Furukawa Electric Co Ltd:The | 光導波路、光導波路モジュールおよび光導波路の作成方法 |
| PL2348114T3 (pl) | 2004-04-21 | 2019-08-30 | Alexion Pharmaceuticals, Inc. | Koniugaty do dostarczania do kości i sposób ich wykorzystania do nakierowywania białek na kość |
| US20070081984A1 (en) | 2005-10-11 | 2007-04-12 | Shunji Tomatsu | Compositions and methods for treating hypophosphatasia |
| CN101068575A (zh) | 2004-12-01 | 2007-11-07 | 建新公司 | 向肝脏定向递送遗传物质的方法 |
| AR063384A1 (es) * | 2006-10-25 | 2009-01-28 | Amgen Inc | Agentes terapeuticos a base de peptidos derivados de toxinas |
| US20080181903A1 (en) | 2006-12-21 | 2008-07-31 | Pdl Biopharma, Inc. | Conjugate of natriuretic peptide and antibody constant region |
| RS53302B (sr) * | 2007-05-11 | 2014-08-29 | Alexion Pharma Holding | Alkalna fosfataza koja je usmerena na kosti, pribor i postupci upotrebe |
| US20100310561A1 (en) | 2007-06-06 | 2010-12-09 | Boehringer Ingelheim International Gmbh | Natriuretic fusion proteins |
| AU2008279379B2 (en) | 2007-07-20 | 2016-03-24 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptides |
| WO2009033680A2 (en) * | 2007-09-11 | 2009-03-19 | Mondobiotech Laboratories Ag | Galanin-like peptide alone or in combination with cyclo-argd as a therapeutic agent |
| EP2217620A2 (en) | 2007-11-21 | 2010-08-18 | BioMarin Pharmaceutical Inc. | Variants of c-type natriuretic peptide |
| HUE032582T2 (en) | 2009-05-20 | 2017-09-28 | Biomarin Pharm Inc | Variants of c-type natriuretic peptide |
-
2012
- 2012-05-22 SG SG11201401605QA patent/SG11201401605QA/en unknown
- 2012-05-22 WO PCT/US2012/039004 patent/WO2013058833A1/en not_active Ceased
- 2012-05-22 CA CA2852874A patent/CA2852874A1/en not_active Abandoned
- 2012-05-22 KR KR1020147013214A patent/KR20140084201A/ko not_active Withdrawn
- 2012-10-18 EP EP18201378.9A patent/EP3488861B1/en active Active
- 2012-10-18 WO PCT/US2012/060869 patent/WO2013059491A1/en not_active Ceased
- 2012-10-18 HK HK15101938.6A patent/HK1201446A1/xx unknown
- 2012-10-18 ES ES18201378T patent/ES2944087T3/es active Active
- 2012-10-18 JP JP2014537254A patent/JP6118807B2/ja active Active
- 2012-10-18 ES ES12842640T patent/ES2714406T3/es active Active
- 2012-10-18 EP EP12842640.0A patent/EP2768526B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP3488861B1 (en) | 2023-02-15 |
| EP2768526B1 (en) | 2018-12-05 |
| HK1201446A1 (en) | 2015-09-04 |
| WO2013058833A8 (en) | 2013-06-13 |
| SG11201401605QA (en) | 2014-09-26 |
| EP3488861A1 (en) | 2019-05-29 |
| CA2852874A1 (en) | 2013-04-25 |
| WO2013058833A1 (en) | 2013-04-25 |
| ES2944087T3 (es) | 2023-06-19 |
| KR20140084201A (ko) | 2014-07-04 |
| EP2768526A1 (en) | 2014-08-27 |
| ES2714406T3 (es) | 2019-05-28 |
| WO2013059491A1 (en) | 2013-04-25 |
| EP2768526A4 (en) | 2015-04-15 |
| JP2015502336A (ja) | 2015-01-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10052366B2 (en) | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof | |
| EP2768526B1 (en) | Compositions comprising alkaline phosphatase and/or natriuretic peptide and methods of use thereof | |
| JP6055779B2 (ja) | ナトリウム利尿ペプチドを含む組成物およびその使用方法 | |
| CN108699120B (zh) | 用于延长蛋白质半衰期的方法 | |
| CA2686803C (en) | Unacylated ghrelin as therapeutic agent in the treatment of metabolic disorders | |
| TW201100092A (en) | Variants of C-type natriuretic peptide | |
| US20080293632A1 (en) | Use of natriuretic peptides for the treatment of stature disorders related to shox gene | |
| KR20120082909A (ko) | 합성 마이오스타틴 펩티드 길항제 | |
| EP2165716A1 (en) | Novel bone mass increasing agent | |
| AU2019406214A1 (en) | Use of annexins in preventing and treating muscle membrane injury | |
| JP2023528709A (ja) | バリアントａｃｔｒｉｉｂタンパク質およびその使用 | |
| JP6025002B2 (ja) | 骨形成または血管新生促進用ペプチドｂｆｐ４およびその用途 | |
| JP2014508765A (ja) | 副甲状腺ホルモン類似体、組成物およびその使用 | |
| EP2556839B1 (en) | Pharmaceutical composition for preventing or treating heart failure and method for screening agent for preventing or treating heart failure | |
| CA3219138A1 (en) | Polypeptides related to hmgb1 useful for promoting tissue regeneration, compositions comprising same, and uses thereof | |
| US20260091078A1 (en) | Oligopeptide that inhibits angiogenesis and vascular function | |
| WO2013152026A1 (en) | Use of apolipoprotein a-1 for promoting bone formation | |
| KR20240134891A (ko) | Gip, glp-1 및 glp-2의 펩티드 삼중 작용제 | |
| Nagpal | The Role of the Ubiquitin Ligase Nedd4-1 in Skeletal Muscle Atrophy | |
| KR20090030070A (ko) | 지방체 이동 신호 펩타이드 및 이를 이용하여 이종단백질을 지방체로 이동시키는 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140926 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151016 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151016 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20160414 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160414 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160802 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161027 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170202 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170307 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170327 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6118807 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |