CA2982237A1 - Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor - Google Patents
Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor Download PDFInfo
- Publication number
- CA2982237A1 CA2982237A1 CA2982237A CA2982237A CA2982237A1 CA 2982237 A1 CA2982237 A1 CA 2982237A1 CA 2982237 A CA2982237 A CA 2982237A CA 2982237 A CA2982237 A CA 2982237A CA 2982237 A1 CA2982237 A1 CA 2982237A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- sequence
- antigen
- nos
- antibody
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 113
- 102000037280 Growth Differentiation Factor 2 Human genes 0.000 title description 295
- 108010090290 Growth Differentiation Factor 2 Proteins 0.000 title description 295
- 230000008685 targeting Effects 0.000 title description 2
- 230000027455 binding Effects 0.000 claims abstract description 628
- 238000009739 binding Methods 0.000 claims abstract description 628
- 239000000427 antigen Substances 0.000 claims abstract description 495
- 108091007433 antigens Proteins 0.000 claims abstract description 494
- 102000036639 antigens Human genes 0.000 claims abstract description 494
- 239000012634 fragment Substances 0.000 claims abstract description 468
- 101000893585 Homo sapiens Growth/differentiation factor 2 Proteins 0.000 claims abstract description 142
- 102000046041 human GDF2 Human genes 0.000 claims abstract description 134
- 239000000203 mixture Substances 0.000 claims abstract description 22
- 241000282414 Homo sapiens Species 0.000 claims description 163
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 147
- 108090000623 proteins and genes Proteins 0.000 claims description 104
- 102000004169 proteins and genes Human genes 0.000 claims description 84
- 150000007523 nucleic acids Chemical group 0.000 claims description 79
- 150000001413 amino acids Chemical class 0.000 claims description 71
- 102000039446 nucleic acids Human genes 0.000 claims description 60
- 108020004707 nucleic acids Proteins 0.000 claims description 60
- 102000040430 polynucleotide Human genes 0.000 claims description 58
- 108091033319 polynucleotide Proteins 0.000 claims description 58
- 239000002157 polynucleotide Substances 0.000 claims description 58
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 54
- 239000003814 drug Substances 0.000 claims description 50
- 125000000539 amino acid group Chemical group 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 36
- 239000013598 vector Substances 0.000 claims description 34
- 208000019423 liver disease Diseases 0.000 claims description 31
- 230000007882 cirrhosis Effects 0.000 claims description 26
- -1 e.g. Proteins 0.000 claims description 26
- 229940124597 therapeutic agent Drugs 0.000 claims description 25
- 206010020772 Hypertension Diseases 0.000 claims description 23
- 230000035772 mutation Effects 0.000 claims description 23
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 23
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 23
- 210000004185 liver Anatomy 0.000 claims description 22
- 210000003240 portal vein Anatomy 0.000 claims description 22
- 239000012636 effector Substances 0.000 claims description 21
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 241001529936 Murinae Species 0.000 claims description 18
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 102000045896 human BMP2 Human genes 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 claims description 12
- 102000046107 human BMP7 Human genes 0.000 claims description 12
- 208000015181 infectious disease Diseases 0.000 claims description 12
- 238000002560 therapeutic procedure Methods 0.000 claims description 12
- 102100040892 Growth/differentiation factor 2 Human genes 0.000 claims description 10
- 101000695367 Homo sapiens Bone morphogenetic protein 10 Proteins 0.000 claims description 10
- 102000052974 human BMP10 Human genes 0.000 claims description 10
- 108010051765 Type I Bone Morphogenetic Protein Receptors Proteins 0.000 claims description 9
- 102000019044 Type I Bone Morphogenetic Protein Receptors Human genes 0.000 claims description 9
- 239000003053 toxin Substances 0.000 claims description 9
- 231100000765 toxin Toxicity 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 102000005962 receptors Human genes 0.000 claims description 7
- 108020003175 receptors Proteins 0.000 claims description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 6
- 201000011374 Alagille syndrome Diseases 0.000 claims description 6
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 6
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 6
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 6
- 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 claims description 6
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 6
- 102000012437 Copper-Transporting ATPases Human genes 0.000 claims description 6
- 208000018565 Hemochromatosis Diseases 0.000 claims description 6
- 241000711549 Hepacivirus C Species 0.000 claims description 6
- 208000037221 Hepatic congestion Diseases 0.000 claims description 6
- 241000700721 Hepatitis B virus Species 0.000 claims description 6
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 6
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 6
- 108010063130 Type II Bone Morphogenetic Protein Receptors Proteins 0.000 claims description 6
- 208000018839 Wilson disease Diseases 0.000 claims description 6
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims description 6
- 239000004148 curcumin Substances 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 6
- 201000000742 primary sclerosing cholangitis Diseases 0.000 claims description 6
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- 208000010706 fatty liver disease Diseases 0.000 claims description 5
- 229940127121 immunoconjugate Drugs 0.000 claims description 5
- 102100025423 Bone morphogenetic protein receptor type-1A Human genes 0.000 claims description 4
- 101000799140 Homo sapiens Activin receptor type-1 Proteins 0.000 claims description 4
- 101000934638 Homo sapiens Bone morphogenetic protein receptor type-1A Proteins 0.000 claims description 4
- 230000003510 anti-fibrotic effect Effects 0.000 claims description 4
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 claims description 4
- 150000003384 small molecules Chemical class 0.000 claims description 4
- 108010050904 Interferons Proteins 0.000 claims description 3
- 102000014150 Interferons Human genes 0.000 claims description 3
- 108020004459 Small interfering RNA Proteins 0.000 claims description 3
- 229930003427 Vitamin E Natural products 0.000 claims description 3
- 229960001997 adefovir Drugs 0.000 claims description 3
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 3
- 230000002424 anti-apoptotic effect Effects 0.000 claims description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
- 230000000713 anti-steatotic effect Effects 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 3
- PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 claims description 3
- 229950011033 cenicriviroc Drugs 0.000 claims description 3
- 239000003246 corticosteroid Substances 0.000 claims description 3
- 229960000980 entecavir Drugs 0.000 claims description 3
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 claims description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 3
- AFLFKFHDSCQHOL-IZZDOVSWSA-N gft505 Chemical compound C1=CC(SC)=CC=C1C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1 AFLFKFHDSCQHOL-IZZDOVSWSA-N 0.000 claims description 3
- 230000002443 hepatoprotective effect Effects 0.000 claims description 3
- 229940079322 interferon Drugs 0.000 claims description 3
- 229960001627 lamivudine Drugs 0.000 claims description 3
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 3
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 3
- 229960003105 metformin Drugs 0.000 claims description 3
- ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 claims description 3
- 229960001601 obeticholic acid Drugs 0.000 claims description 3
- 229960005095 pioglitazone Drugs 0.000 claims description 3
- 229960002091 simeprevir Drugs 0.000 claims description 3
- JTZZSQYMACOLNN-VDWJNHBNSA-N simeprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCN(C)C(=O)[C@H]1[C@H](C(N2)=O)C[C@H](C1)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(C)C)C)OC)NS(=O)(=O)C1CC1 JTZZSQYMACOLNN-VDWJNHBNSA-N 0.000 claims description 3
- 229960002935 telaprevir Drugs 0.000 claims description 3
- 108010017101 telaprevir Proteins 0.000 claims description 3
- BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 claims description 3
- 229960004556 tenofovir Drugs 0.000 claims description 3
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims description 3
- 229940046009 vitamin E Drugs 0.000 claims description 3
- 235000019165 vitamin E Nutrition 0.000 claims description 3
- 239000011709 vitamin E Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 102100034111 Activin receptor type-1 Human genes 0.000 claims 2
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims 2
- 210000004027 cell Anatomy 0.000 description 122
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 85
- 235000018102 proteins Nutrition 0.000 description 81
- 235000001014 amino acid Nutrition 0.000 description 76
- 229940024606 amino acid Drugs 0.000 description 72
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 54
- 108090000765 processed proteins & peptides Proteins 0.000 description 54
- 102000004196 processed proteins & peptides Human genes 0.000 description 46
- 229920001184 polypeptide Polymers 0.000 description 38
- 238000012360 testing method Methods 0.000 description 36
- 230000014509 gene expression Effects 0.000 description 34
- 238000003556 assay Methods 0.000 description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
- 210000004602 germ cell Anatomy 0.000 description 31
- 108020004414 DNA Proteins 0.000 description 28
- 206010016654 Fibrosis Diseases 0.000 description 28
- 108060003951 Immunoglobulin Proteins 0.000 description 28
- 102000018358 immunoglobulin Human genes 0.000 description 28
- 238000001727 in vivo Methods 0.000 description 27
- 230000006870 function Effects 0.000 description 26
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 230000026731 phosphorylation Effects 0.000 description 22
- 238000006366 phosphorylation reaction Methods 0.000 description 22
- 230000006698 induction Effects 0.000 description 21
- 101710118482 Bone morphogenetic protein 10 Proteins 0.000 description 20
- 102100028726 Bone morphogenetic protein 10 Human genes 0.000 description 20
- 102100025744 Mothers against decapentaplegic homolog 1 Human genes 0.000 description 20
- 101700032040 SMAD1 Proteins 0.000 description 20
- 230000004048 modification Effects 0.000 description 20
- 238000012986 modification Methods 0.000 description 20
- 201000010099 disease Diseases 0.000 description 19
- 239000013604 expression vector Substances 0.000 description 19
- 230000003176 fibrotic effect Effects 0.000 description 19
- 238000000338 in vitro Methods 0.000 description 19
- 238000006467 substitution reaction Methods 0.000 description 19
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 18
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 18
- 230000004761 fibrosis Effects 0.000 description 18
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 17
- 238000005516 engineering process Methods 0.000 description 17
- 229920001223 polyethylene glycol Polymers 0.000 description 17
- 239000002202 Polyethylene glycol Substances 0.000 description 16
- 238000013459 approach Methods 0.000 description 16
- 125000003729 nucleotide group Chemical group 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- 239000002773 nucleotide Substances 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 230000000670 limiting effect Effects 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 13
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 13
- 108020004705 Codon Proteins 0.000 description 13
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 12
- 230000013595 glycosylation Effects 0.000 description 12
- 238000006206 glycosylation reaction Methods 0.000 description 12
- 210000005229 liver cell Anatomy 0.000 description 12
- 238000010172 mouse model Methods 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 11
- 238000002965 ELISA Methods 0.000 description 11
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 11
- 238000007792 addition Methods 0.000 description 11
- 230000000890 antigenic effect Effects 0.000 description 11
- 230000000295 complement effect Effects 0.000 description 11
- 238000012217 deletion Methods 0.000 description 11
- 230000037430 deletion Effects 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000003993 interaction Effects 0.000 description 11
- 238000002703 mutagenesis Methods 0.000 description 11
- 231100000350 mutagenesis Toxicity 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 10
- 208000036449 fibrotic liver disease Diseases 0.000 description 10
- 210000004408 hybridoma Anatomy 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 102000009109 Fc receptors Human genes 0.000 description 9
- 108010087819 Fc receptors Proteins 0.000 description 9
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 9
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- 108020001507 fusion proteins Proteins 0.000 description 9
- 102000037865 fusion proteins Human genes 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 9
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 8
- 206010067125 Liver injury Diseases 0.000 description 8
- 230000021615 conjugation Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- 231100000234 hepatic damage Toxicity 0.000 description 8
- 229940050526 hydroxyethylstarch Drugs 0.000 description 8
- 230000008818 liver damage Effects 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 238000000159 protein binding assay Methods 0.000 description 8
- 238000012216 screening Methods 0.000 description 8
- 230000011664 signaling Effects 0.000 description 8
- 239000007790 solid phase Substances 0.000 description 8
- 230000009261 transgenic effect Effects 0.000 description 8
- 239000003623 enhancer Substances 0.000 description 7
- 210000004962 mammalian cell Anatomy 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 108010088751 Albumins Proteins 0.000 description 6
- 102000009027 Albumins Human genes 0.000 description 6
- 102000016359 Fibronectins Human genes 0.000 description 6
- 108010067306 Fibronectins Proteins 0.000 description 6
- 102100030610 Mothers against decapentaplegic homolog 5 Human genes 0.000 description 6
- 101710143113 Mothers against decapentaplegic homolog 5 Proteins 0.000 description 6
- 101100175311 Mus musculus Gdf2 gene Proteins 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 230000009870 specific binding Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 206010069754 Acquired gene mutation Diseases 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108050006654 Lipocalin Proteins 0.000 description 5
- 102000019298 Lipocalin Human genes 0.000 description 5
- 101700031501 SMAD9 Proteins 0.000 description 5
- 102000049870 Smad8 Human genes 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 150000001720 carbohydrates Chemical class 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 230000001268 conjugating effect Effects 0.000 description 5
- 210000002808 connective tissue Anatomy 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 229940072221 immunoglobulins Drugs 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 238000003127 radioimmunoassay Methods 0.000 description 5
- 238000003571 reporter gene assay Methods 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000037439 somatic mutation Effects 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 102000008102 Ankyrins Human genes 0.000 description 4
- 108010049777 Ankyrins Proteins 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 102000002090 Fibronectin type III Human genes 0.000 description 4
- 108050009401 Fibronectin type III Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 4
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 231100000599 cytotoxic agent Toxicity 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 210000001508 eye Anatomy 0.000 description 4
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 4
- 238000002825 functional assay Methods 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
- 229930182817 methionine Chemical group 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 238000011275 oncology therapy Methods 0.000 description 4
- 230000006320 pegylation Effects 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 241000282836 Camelus dromedarius Species 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 101000934635 Homo sapiens Bone morphogenetic protein receptor type-2 Proteins 0.000 description 3
- 238000012450 HuMAb Mouse Methods 0.000 description 3
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 3
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- 241000282842 Lama glama Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 102000007374 Smad Proteins Human genes 0.000 description 3
- 108010007945 Smad Proteins Proteins 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 108090000848 Ubiquitin Proteins 0.000 description 3
- 102000044159 Ubiquitin Human genes 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000009830 antibody antigen interaction Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000008512 biological response Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 230000003908 liver function Effects 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 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 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- VXPSQDAMFATNNG-UHFFFAOYSA-N 3-[2-(2,5-dioxopyrrol-3-yl)phenyl]pyrrole-2,5-dione Chemical compound O=C1NC(=O)C(C=2C(=CC=CC=2)C=2C(NC(=O)C=2)=O)=C1 VXPSQDAMFATNNG-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 101710189812 Bilin-binding protein Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000020446 Cardiac disease Diseases 0.000 description 2
- 101710112752 Cytotoxin Proteins 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 201000003066 Diffuse Scleroderma Diseases 0.000 description 2
- RNPABQVCNAUEIY-GUQYYFCISA-N Germine Chemical compound O1[C@@]([C@H](CC[C@]23C)O)(O)[C@H]3C[C@@H](O)[C@@H]([C@]3(O)[C@@H](O)[C@H](O)[C@@H]4[C@]5(C)O)[C@@]12C[C@H]3[C@@H]4CN1[C@H]5CC[C@H](C)C1 RNPABQVCNAUEIY-GUQYYFCISA-N 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101710204270 Growth/differentiation factor 2 Proteins 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
- 101000970954 Homo sapiens Activin receptor type-2A Proteins 0.000 description 2
- 101000937269 Homo sapiens Activin receptor type-2B Proteins 0.000 description 2
- 101000799194 Homo sapiens Serine/threonine-protein kinase receptor R3 Proteins 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
- 208000024934 IgG4-related mediastinitis Diseases 0.000 description 2
- 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 description 2
- 108010029660 Intrinsically Disordered Proteins Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000012449 Kunming mouse Methods 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 208000002805 Mediastinal fibrosis Diseases 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 241000255972 Pieris <butterfly> Species 0.000 description 2
- 206010036805 Progressive massive fibrosis Diseases 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 2
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 241000710961 Semliki Forest virus Species 0.000 description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 description 2
- 206010042953 Systemic sclerosis Diseases 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 230000009824 affinity maturation Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 239000002619 cytotoxin Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 239000012893 effector ligand Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 201000010048 endomyocardial fibrosis Diseases 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- RNPABQVCNAUEIY-UHFFFAOYSA-N germine Natural products O1C(C(CCC23C)O)(O)C3CC(O)C(C3(O)C(O)C(O)C4C5(C)O)C12CC3C4CN1C5CCC(C)C1 RNPABQVCNAUEIY-UHFFFAOYSA-N 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 210000004024 hepatic stellate cell Anatomy 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 102000054953 human ACVR1 Human genes 0.000 description 2
- 102000045412 human ACVR2B Human genes 0.000 description 2
- 102000047644 human ACVRL1 Human genes 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000002169 hydrotherapy Methods 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000009149 molecular binding Effects 0.000 description 2
- 238000001823 molecular biology technique Methods 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 230000010807 negative regulation of binding Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 239000006152 selective media Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000009772 tissue formation Effects 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- 238000012448 transchromosomic mouse model Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 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 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 208000016261 weight loss Diseases 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- JBDOSUUXMYMWQH-UHFFFAOYSA-N 1-naphthyl isothiocyanate Chemical compound C1=CC=C2C(N=C=S)=CC=CC2=C1 JBDOSUUXMYMWQH-UHFFFAOYSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- PINRUEQFGKWBTO-UHFFFAOYSA-N 3-methyl-5-phenyl-1,3-oxazolidin-2-imine Chemical compound O1C(=N)N(C)CC1C1=CC=CC=C1 PINRUEQFGKWBTO-UHFFFAOYSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 102000052866 Amino Acyl-tRNA Synthetases Human genes 0.000 description 1
- 108700028939 Amino Acyl-tRNA Synthetases Proteins 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 101150061927 BMP2 gene Proteins 0.000 description 1
- 101150018057 BMP7 gene Proteins 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 108091028026 C-DNA Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282828 Camelus bactrianus Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000016362 Catenins Human genes 0.000 description 1
- 108010067316 Catenins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 206010057573 Chronic hepatic failure Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102000014824 Crystallins Human genes 0.000 description 1
- 108010064003 Crystallins Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 235000017274 Diospyros sandwicensis Nutrition 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 101710089384 Extracellular protease Proteins 0.000 description 1
- 206010049811 Extraskeletal ossification Diseases 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 102000006471 Fucosyltransferases Human genes 0.000 description 1
- 108010019236 Fucosyltransferases Proteins 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 208000034970 Heterotopic Ossification Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101710182312 High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 102100026119 High affinity immunoglobulin gamma Fc receptor IB Human genes 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 101150047694 ID1 gene Proteins 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical group OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical group C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Chemical group CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 101710122625 Low affinity immunoglobulin gamma Fc region receptor II Proteins 0.000 description 1
- 101710177649 Low affinity immunoglobulin gamma Fc region receptor III Proteins 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- ZOKXTWBITQBERF-AKLPVKDBSA-N Molybdenum Mo-99 Chemical compound [99Mo] ZOKXTWBITQBERF-AKLPVKDBSA-N 0.000 description 1
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 1
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 1
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 1
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 208000003510 Nephrogenic Fibrosing Dermopathy Diseases 0.000 description 1
- 206010058116 Nephrogenic anaemia Diseases 0.000 description 1
- 206010067467 Nephrogenic systemic fibrosis Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000004362 Penile Induration Diseases 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 206010062070 Peritonitis bacterial Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 208000020758 Peyronie disease Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 241000255969 Pieris brassicae Species 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 1
- 101710202113 Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 201000002154 Pterygium Diseases 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 102000042463 Rho family Human genes 0.000 description 1
- 108091078243 Rho family Proteins 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 206010050207 Skin fibrosis Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 101710192266 Tegument protein VP22 Proteins 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 206010065584 Urethral stenosis Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000282840 Vicugna vicugna Species 0.000 description 1
- 102100035071 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000012452 Xenomouse strains Methods 0.000 description 1
- FHNFHKCVQCLJFQ-NJFSPNSNSA-N Xenon-133 Chemical compound [133Xe] FHNFHKCVQCLJFQ-NJFSPNSNSA-N 0.000 description 1
- SWPYNTWPIAZGLT-UHFFFAOYSA-N [amino(ethoxy)phosphanyl]oxyethane Chemical compound CCOP(N)OCC SWPYNTWPIAZGLT-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 208000010123 anthracosis Diseases 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 208000006722 brachydactyly type A2 Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 208000017760 chronic graft versus host disease Diseases 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 231100000409 cytocidal Toxicity 0.000 description 1
- 230000000445 cytocidal effect Effects 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002446 fucosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)[C@@H](O1)C)* 0.000 description 1
- 101150023212 fut8 gene Proteins 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 102000013069 gamma-Crystallins Human genes 0.000 description 1
- 108010079934 gamma-Crystallins Proteins 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002337 glycosamines Chemical group 0.000 description 1
- 108700014210 glycosyltransferase activity proteins Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 230000028974 hepatocyte apoptotic process Effects 0.000 description 1
- 201000004515 hepatopulmonary syndrome Diseases 0.000 description 1
- 201000011200 hepatorenal syndrome Diseases 0.000 description 1
- 102000018511 hepcidin Human genes 0.000 description 1
- 108060003558 hepcidin Proteins 0.000 description 1
- 229940066919 hepcidin Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 210000000688 human artificial chromosome Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000001459 mortal effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- 210000000651 myofibroblast Anatomy 0.000 description 1
- ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029964 regulation of glucose metabolic process Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000013424 sirius red staining Methods 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014723 transformation of host cell by virus Effects 0.000 description 1
- 238000012451 transgenic animal system Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 201000001988 urethral stricture Diseases 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 229950004094 xenon (133xe) Drugs 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- 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
- A61K38/18—Growth factors; Growth regulators
- A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Mycology (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNPCT/CN2015/080887 | 2015-06-05 | ||
| CN2015080887 | 2015-06-05 | ||
| PCT/IB2016/053095 WO2016193872A2 (en) | 2015-06-05 | 2016-05-26 | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2982237A1 true CA2982237A1 (en) | 2016-12-08 |
Family
ID=56096674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2982237A Abandoned CA2982237A1 (en) | 2015-06-05 | 2016-05-26 | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US10047155B2 (enExample) |
| EP (1) | EP3303387A2 (enExample) |
| JP (1) | JP2018522540A (enExample) |
| KR (1) | KR20180014714A (enExample) |
| CN (1) | CN107614526A (enExample) |
| AR (1) | AR104906A1 (enExample) |
| AU (1) | AU2016273028B2 (enExample) |
| BR (1) | BR112017021484A2 (enExample) |
| CA (1) | CA2982237A1 (enExample) |
| CL (1) | CL2017002705A1 (enExample) |
| CO (1) | CO2017011512A2 (enExample) |
| CR (1) | CR20170554A (enExample) |
| EA (1) | EA201792561A1 (enExample) |
| EC (1) | ECSP17080733A (enExample) |
| HK (1) | HK1249537A1 (enExample) |
| IL (1) | IL254837A0 (enExample) |
| MX (1) | MX2017015690A (enExample) |
| PE (1) | PE20180041A1 (enExample) |
| PH (1) | PH12017502020A1 (enExample) |
| SG (1) | SG11201707815RA (enExample) |
| TN (1) | TN2017000417A1 (enExample) |
| TW (1) | TW201716438A (enExample) |
| UY (1) | UY36706A (enExample) |
| WO (1) | WO2016193872A2 (enExample) |
| ZA (1) | ZA201805721B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017189964A2 (en) | 2016-04-29 | 2017-11-02 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| US11326182B2 (en) | 2016-04-29 | 2022-05-10 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| CN106994181A (zh) * | 2017-03-10 | 2017-08-01 | 上海交通大学医学院附属第九人民医院 | Bmp9在制备延缓肝纤维化药物中的应用 |
| CN107760779B (zh) * | 2017-11-03 | 2020-10-16 | 中国医学科学院阜外医院 | 肺动脉高压相关的突变型bmp9基因及其应用 |
| JP2023507364A (ja) | 2019-12-20 | 2023-02-22 | ノバルティス アーゲー | インテグリン阻害剤を使用する肝疾患の治療の組み合わせ |
| WO2022101853A1 (en) | 2020-11-16 | 2022-05-19 | Novartis Ag | Method of determining liver fibrosis |
| KR102780923B1 (ko) * | 2021-10-22 | 2025-03-17 | 고려대학교 산학협력단 | Bmp 유래 신규 펩타이드 및 이의 용도 |
| WO2023233330A1 (en) | 2022-05-31 | 2023-12-07 | Pfizer Inc. | Anti-bmp9 antibodies and methods of use thereof |
| CN115040638A (zh) * | 2022-06-14 | 2022-09-13 | 上海市东方医院(同济大学附属东方医院) | Bmp9在制备mafld、nash、nash相关肝纤维化/肝硬化的药物中的用途 |
| CN116058335B (zh) * | 2022-11-25 | 2025-07-25 | 中国医学科学院阜外医院 | 一种自发强直性脊柱炎模型的构建方法和应用 |
| CN116115736A (zh) * | 2022-12-09 | 2023-05-16 | 上海交通大学医学院附属瑞金医院 | 一种bmp9在制备抑制成骨细胞衰老的制剂或药物中的应用 |
| WO2025149667A1 (en) | 2024-01-12 | 2025-07-17 | Pheon Therapeutics Ltd | Antibody drug conjugates and uses thereof |
Family Cites Families (134)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4708871A (en) | 1983-03-08 | 1987-11-24 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US4881175A (en) | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
| AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
| US5013653A (en) | 1987-03-20 | 1991-05-07 | Creative Biomolecules, Inc. | Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| DE3853515T3 (de) | 1987-05-21 | 2005-08-25 | Micromet Ag | Multifunktionelle proteine mit vorbestimmter zielsetzung. |
| US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| US5336603A (en) | 1987-10-02 | 1994-08-09 | Genentech, Inc. | CD4 adheson variants |
| US5476996A (en) | 1988-06-14 | 1995-12-19 | Lidak Pharmaceuticals | Human immune system in non-human animal |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| KR900005995A (ko) | 1988-10-31 | 1990-05-07 | 우메모또 요시마사 | 변형 인터류킨-2 및 그의 제조방법 |
| EP0401384B1 (en) | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5112946A (en) | 1989-07-06 | 1992-05-12 | Repligen Corporation | Modified pf4 compositions and methods of use |
| FR2650598B1 (fr) | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| WO1991006570A1 (en) | 1989-10-25 | 1991-05-16 | The University Of Melbourne | HYBRID Fc RECEPTOR MOLECULES |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5349053A (en) | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
| US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| AU643109B2 (en) | 1990-12-14 | 1993-11-04 | Cell Genesys, Inc. | Chimeric chains for receptor-associated signal transduction pathways |
| US6287816B1 (en) | 1991-06-25 | 2001-09-11 | Genetics Institute, Inc. | BMP-9 compositions |
| US5661007A (en) | 1991-06-25 | 1997-08-26 | Genetics Institute, Inc. | Bone morphogenetic protein-9 compositions |
| ATE408012T1 (de) | 1991-12-02 | 2008-09-15 | Medical Res Council | Herstellung von autoantikörpern auf phagenoberflächen ausgehend von antikörpersegmentbibliotheken |
| DE69233204T2 (de) | 1991-12-13 | 2004-07-15 | Xoma Corp., Berkeley | Verfahren und materialien zur herstellung von modifizierten variablen antikörperdomänen und ihre therapeutische verwendung |
| CA2124967C (en) | 1991-12-17 | 2008-04-08 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| FR2686901A1 (fr) | 1992-01-31 | 1993-08-06 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides antithrombotiques, leur preparation et compositions pharmaceutiques les contenant. |
| US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
| US5447851B1 (en) | 1992-04-02 | 1999-07-06 | Univ Texas System Board Of | Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells |
| CA2118508A1 (en) | 1992-04-24 | 1993-11-11 | Elizabeth S. Ward | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
| EP0656946B2 (en) | 1992-08-21 | 2010-03-31 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1994029351A2 (en) | 1993-06-16 | 1994-12-22 | Celltech Limited | Antibodies |
| SE9400088D0 (sv) | 1994-01-14 | 1994-01-14 | Kabi Pharmacia Ab | Bacterial receptor structures |
| US5834252A (en) | 1995-04-18 | 1998-11-10 | Glaxo Group Limited | End-complementary polymerase reaction |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| AU3382595A (en) | 1994-07-29 | 1996-03-04 | Smithkline Beecham Corporation | Novel compounds |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
| WO1997034631A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
| WO1998023289A1 (en) | 1996-11-27 | 1998-06-04 | The General Hospital Corporation | MODULATION OF IgG BINDING TO FcRn |
| US6423501B2 (en) | 1996-12-13 | 2002-07-23 | Beth Israel Deaconess Medical Center | Calcium-independent negative regulation by CD81 of receptor signaling |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| US6034062A (en) | 1997-03-13 | 2000-03-07 | Genetics Institute, Inc. | Bone morphogenetic protein (BMP)-9 compositions and their uses |
| ES2258817T3 (es) | 1997-05-21 | 2006-09-01 | Biovation Limited | Metodo para la produccion de proteinas no inmunogenas. |
| WO1998056906A1 (en) | 1997-06-11 | 1998-12-17 | Thoegersen Hans Christian | Trimerising module |
| EP0985039B1 (en) | 1997-06-12 | 2008-02-20 | Novartis International Pharmaceutical Ltd. | Artificial antibody polypeptides |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| JP4334141B2 (ja) | 1998-04-20 | 2009-09-30 | グリカート バイオテクノロジー アクチェンゲゼルシャフト | 抗体依存性細胞傷害性を改善するための抗体のグリコシル化操作 |
| US6818418B1 (en) | 1998-12-10 | 2004-11-16 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| BR0008758A (pt) | 1999-01-15 | 2001-12-04 | Genentech Inc | Variantes de polipeptìdeos parentais com funçãoefetora alterada, polipeptìdeos, composição ácidonucleico isolado, vetor, célula hospedeira,método para produzir uma variante depolipeptìdeo, método para o tratamento de umadesordem em mamìferos e método para produziruma região fc variante |
| CA2369292C (en) | 1999-04-09 | 2010-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Method of modulating the activity of functional immune molecules |
| DE19932688B4 (de) | 1999-07-13 | 2009-10-08 | Scil Proteins Gmbh | Design von Beta-Faltblatt-Proteinen des gamma-II-kristallins antikörperähnlichen |
| EP1990409A3 (en) | 1999-07-20 | 2011-05-18 | MorphoSys AG | Bacteriophage |
| EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| CA2405550A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2002057445A1 (en) | 2000-05-26 | 2002-07-25 | National Research Council Of Canada | Single-domain brain-targeting antibody fragments derived from llama antibodies |
| MXPA02012602A (es) | 2000-06-22 | 2003-05-14 | Genentech Inc | Anticuerpos monoclonales agonistas anti-trk-c. |
| DK1354034T3 (da) | 2000-11-30 | 2008-03-25 | Medarex Inc | Transgene transchromosomale gnavere til fremstilling af humane antistoffer |
| US20050048512A1 (en) | 2001-04-26 | 2005-03-03 | Avidia Research Institute | Combinatorial libraries of monomer domains |
| US20040175756A1 (en) | 2001-04-26 | 2004-09-09 | Avidia Research Institute | Methods for using combinatorial libraries of monomer domains |
| US20050053973A1 (en) | 2001-04-26 | 2005-03-10 | Avidia Research Institute | Novel proteins with targeted binding |
| JP2004532038A (ja) | 2001-05-17 | 2004-10-21 | ディヴァーサ コーポレイション | 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 |
| ATE430580T1 (de) | 2001-10-25 | 2009-05-15 | Genentech Inc | Glycoprotein-zusammensetzungen |
| US7771951B2 (en) | 2001-12-03 | 2010-08-10 | Amgen Fremont Inc. | Antibody categorization based on binding characteristics |
| US7335478B2 (en) | 2002-04-18 | 2008-02-26 | Kalobios Pharmaceuticals, Inc. | Reactivation-based molecular interaction sensors |
| US20030157579A1 (en) | 2002-02-14 | 2003-08-21 | Kalobios, Inc. | Molecular sensors activated by disinhibition |
| WO2003074679A2 (en) | 2002-03-01 | 2003-09-12 | Xencor | Antibody optimization |
| US7816497B2 (en) | 2002-10-30 | 2010-10-19 | University Of Kentucky | Compositions and methods for inhibiting drusen complement components C3a and C5a for the treatment of age-related macular degeneration |
| WO2004072266A2 (en) | 2003-02-13 | 2004-08-26 | Kalobios Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
| DE10324447A1 (de) | 2003-05-28 | 2004-12-30 | Scil Proteins Gmbh | Generierung künstlicher Bindungsproteine auf der Grundlage von Ubiquitin |
| US7745585B2 (en) | 2003-09-02 | 2010-06-29 | Boehringer Ingelheim International Gmbh | Antibodies to interleukin-like epithelial-mesenchymal transition inducer (ILEI) |
| AU2004308482A1 (en) | 2003-12-23 | 2005-07-14 | Rinat Neuroscience Corp. | Agonist anti-trkC antibodies and methods using same |
| EP1761561B1 (en) | 2004-01-20 | 2015-08-26 | KaloBios Pharmaceuticals, Inc. | Antibody specificity transfer using minimal essential binding determinants |
| EP1571159A1 (en) | 2004-03-04 | 2005-09-07 | Bayerische Julius-Maximilians-Universität Würzburg | Mutein of a bone morphogenetic protein and use thereof |
| US20060008844A1 (en) | 2004-06-17 | 2006-01-12 | Avidia Research Institute | c-Met kinase binding proteins |
| WO2006016110A1 (en) | 2004-08-10 | 2006-02-16 | University College Cardiff Consultants Limited | Methods and kit for the prognosis of breast cancer |
| JP4696237B2 (ja) | 2005-03-03 | 2011-06-08 | 国立大学法人 岡山大学 | 糖尿病性腎症の治療用医薬組成物 |
| DK1933871T3 (da) | 2005-09-07 | 2013-07-08 | Amgen Fremont Inc | Humane monoklonale antistoffer mod activin-receptor-lignende kinase-1 |
| EP1946765A4 (en) | 2005-09-22 | 2009-10-21 | Keiichi Fukuda | MEANS FOR THE TREATMENT OF ANGIOGENESIS-RELATED DISEASES WITH CHROMDROMODULIN-I AS AN ACTIVE AGENT |
| CN1844391A (zh) | 2006-04-26 | 2006-10-11 | 嘉兴波亿生物科技开发有限公司 | 人骨形态发生蛋白9重组蛋白质核苷酸序列及生产方法和用途 |
| CN105837690A (zh) | 2006-06-12 | 2016-08-10 | 新兴产品开发西雅图有限公司 | 具有效应功能的单链多价结合蛋白 |
| EP1873157A1 (en) | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| US8088895B2 (en) | 2006-10-18 | 2012-01-03 | Chemocentryx, Inc. | Antibodies that bind CXCR7 epitopes |
| WO2008057461A2 (en) * | 2006-11-02 | 2008-05-15 | Acceleron Pharma, Inc. | Alk1 receptor and ligand antagonists and uses thereof |
| US8642031B2 (en) * | 2006-11-02 | 2014-02-04 | Acceleron Pharma, Inc. | Antagonists of BMP9, BMP10, ALK1 and other ALK1 ligands, and uses thereof |
| JP2008225462A (ja) | 2007-02-14 | 2008-09-25 | Asahi Kasei Chemicals Corp | 積層光学フィルム |
| US8318135B2 (en) | 2007-03-19 | 2012-11-27 | National Research Council Of Canada | Antagonist of ligands and uses thereof |
| US20090017019A1 (en) | 2007-06-01 | 2009-01-15 | Wyeth | Methods and compositions for modulating bmp-10 activity |
| CA2724525A1 (en) | 2008-05-15 | 2009-11-19 | Acceleron Pharma, Inc. | Antagonists of bmp9, bmp10, alk1 and other alk1 ligands, and uses thereof |
| WO2010126169A1 (ja) * | 2009-04-30 | 2010-11-04 | 協和発酵キリン株式会社 | Alk1阻害剤を有効成分とする血管障害を抑制するための医薬組成物 |
| EP2427494B1 (en) | 2009-05-08 | 2017-10-18 | Novartis AG | Methods of modulating fibrosis using bone morphogenetic protein-9 (bmp-9) modulators |
| US20160228509A9 (en) * | 2009-05-08 | 2016-08-11 | Novartis Ag | Diagnostic BioMarkers for Fibrotic Disorders |
| PH12013500294A1 (en) | 2010-08-20 | 2017-08-23 | Wyeth Llc | Designer osteogenic proteins |
| CN103476429B (zh) | 2010-09-03 | 2016-08-24 | 施特姆森特克斯股份有限公司 | 新型调节剂及使用方法 |
| FR2971250A1 (fr) | 2011-02-07 | 2012-08-10 | Univ Nantes | Anticorps anti-gb3 utiles dans le traitement des maladies associees a l'angiogenese |
| EP2809335A4 (en) | 2012-02-02 | 2015-10-28 | Acceleron Pharma Inc | ALK1 ANTAGONISTS AND THEIR USE FOR THE TREATMENT OF NIERENZELLENKARZINOMEN |
| US9809636B2 (en) | 2012-04-06 | 2017-11-07 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels comprising administering BMP9 |
| WO2013164689A2 (en) | 2012-05-02 | 2013-11-07 | Lantto, Johan | Humanized pan-her antibody compositions |
| CN103387605B (zh) | 2012-05-08 | 2018-06-12 | 复旦大学 | 一种rtn4b多肽、其单抗、产生单抗的杂交瘤细胞株及他们的制备与应用 |
| CN104411720B (zh) * | 2012-07-02 | 2018-05-11 | 协和发酵麒麟株式会社 | 以抗bmp9抗体作为有效成分的、对肾性贫血、癌性贫血等贫血的治疗剂 |
| FR2993278B1 (fr) | 2012-07-13 | 2016-02-19 | Coatex Sas | Utilisation d'un polymere peigne pour preparer une suspension contenant du carbonate de calcium et presentant une sensibilite a la temperature reduite. |
| WO2014051109A1 (ja) | 2012-09-28 | 2014-04-03 | 協和発酵キリン株式会社 | 抗ヒトbmp9抗体および該抗体を有効成分とする異所性骨化疾患の治療剤 |
| KR20220013459A (ko) * | 2013-10-25 | 2022-02-04 | 악셀레론 파마 인코포레이티드 | 섬유화 질환을 치료하기 위한 엔도글린 펩티드 |
-
2016
- 2016-05-26 CA CA2982237A patent/CA2982237A1/en not_active Abandoned
- 2016-05-26 HK HK18109109.9A patent/HK1249537A1/zh unknown
- 2016-05-26 JP JP2017563165A patent/JP2018522540A/ja active Pending
- 2016-05-26 EP EP16726435.7A patent/EP3303387A2/en not_active Withdrawn
- 2016-05-26 PE PE2017002522A patent/PE20180041A1/es unknown
- 2016-05-26 AU AU2016273028A patent/AU2016273028B2/en not_active Ceased
- 2016-05-26 MX MX2017015690A patent/MX2017015690A/es unknown
- 2016-05-26 BR BR112017021484A patent/BR112017021484A2/pt not_active Application Discontinuation
- 2016-05-26 WO PCT/IB2016/053095 patent/WO2016193872A2/en not_active Ceased
- 2016-05-26 TN TNP/2017/000417A patent/TN2017000417A1/en unknown
- 2016-05-26 EA EA201792561A patent/EA201792561A1/ru unknown
- 2016-05-26 US US15/165,150 patent/US10047155B2/en not_active Expired - Fee Related
- 2016-05-26 KR KR1020177034690A patent/KR20180014714A/ko not_active Withdrawn
- 2016-05-26 SG SG11201707815RA patent/SG11201707815RA/en unknown
- 2016-05-26 CN CN201680032467.1A patent/CN107614526A/zh active Pending
- 2016-05-28 CR CR20170554A patent/CR20170554A/es unknown
- 2016-06-02 UY UY0001036706A patent/UY36706A/es not_active Application Discontinuation
- 2016-06-03 AR ARP160101663A patent/AR104906A1/es unknown
- 2016-06-04 TW TW105117773A patent/TW201716438A/zh unknown
-
2017
- 2017-10-02 IL IL254837A patent/IL254837A0/en unknown
- 2017-10-25 CL CL2017002705A patent/CL2017002705A1/es unknown
- 2017-11-07 PH PH12017502020A patent/PH12017502020A1/en unknown
- 2017-11-09 CO CONC2017/0011512A patent/CO2017011512A2/es unknown
- 2017-12-05 EC ECIEPI201780733A patent/ECSP17080733A/es unknown
-
2018
- 2018-07-05 US US16/027,954 patent/US20190153084A1/en not_active Abandoned
- 2018-08-27 ZA ZA201805721A patent/ZA201805721B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SG11201707815RA (en) | 2017-12-28 |
| AR104906A1 (es) | 2017-08-23 |
| US20190153084A1 (en) | 2019-05-23 |
| ZA201805721B (en) | 2019-11-27 |
| CR20170554A (es) | 2018-02-06 |
| TN2017000417A1 (en) | 2019-01-16 |
| AU2016273028B2 (en) | 2019-02-14 |
| JP2018522540A (ja) | 2018-08-16 |
| EP3303387A2 (en) | 2018-04-11 |
| PH12017502020A1 (en) | 2018-04-02 |
| PE20180041A1 (es) | 2018-01-09 |
| WO2016193872A3 (en) | 2017-03-30 |
| ECSP17080733A (es) | 2019-03-29 |
| CN107614526A (zh) | 2018-01-19 |
| MX2017015690A (es) | 2018-07-06 |
| IL254837A0 (en) | 2017-12-31 |
| US10047155B2 (en) | 2018-08-14 |
| KR20180014714A (ko) | 2018-02-09 |
| US20160355583A1 (en) | 2016-12-08 |
| CL2017002705A1 (es) | 2018-03-23 |
| UY36706A (es) | 2016-12-30 |
| TW201716438A (zh) | 2017-05-16 |
| HK1249537A1 (zh) | 2018-11-02 |
| CO2017011512A2 (es) | 2018-01-31 |
| EA201792561A1 (ru) | 2018-04-30 |
| AU2016273028A1 (en) | 2017-10-12 |
| BR112017021484A2 (pt) | 2018-07-03 |
| WO2016193872A2 (en) | 2016-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2016273028B2 (en) | Antibodies targeting bone morphogenetic protein 9 (BMP9) and methods therefor | |
| US11530261B2 (en) | Compositions and methods for antibodies targeting BMP6 | |
| US8241628B2 (en) | Compositions and methods for antibodies targeting complement protein C5 | |
| AU2017245335B2 (en) | Lectin-like oxidized LDL receptor 1 antibodies and methods of use | |
| EP2427491A2 (en) | Compositions and methods for antibodies targeting complement protein c3b | |
| WO2012172495A1 (en) | Compositions and methods for antibodies targeting tem8 | |
| AU2014224144A1 (en) | Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (LRP6) antibodies | |
| AU2017283787A1 (en) | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (BMP6) | |
| US20200010542A1 (en) | Antibodies for il-17c | |
| EA039579B1 (ru) | Способы и композиции антител, направленных против bmp6 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220816 |
|
| FZDE | Discontinued |
Effective date: 20220816 |