NL2013007B1 - Methods of treating TTP with immunoglobulin single variable domains and uses thereof. - Google Patents
Methods of treating TTP with immunoglobulin single variable domains and uses thereof. Download PDFInfo
- Publication number
- NL2013007B1 NL2013007B1 NL2013007A NL2013007A NL2013007B1 NL 2013007 B1 NL2013007 B1 NL 2013007B1 NL 2013007 A NL2013007 A NL 2013007A NL 2013007 A NL2013007 A NL 2013007A NL 2013007 B1 NL2013007 B1 NL 2013007B1
- Authority
- NL
- Netherlands
- Prior art keywords
- polypeptide
- amino acid
- vwf
- acid sequence
- ttp
- Prior art date
Links
- 108060003951 Immunoglobulin Proteins 0.000 title claims abstract description 73
- 102000018358 immunoglobulin Human genes 0.000 title claims abstract description 73
- 238000000034 method Methods 0.000 title description 79
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 299
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 297
- 229920001184 polypeptide Polymers 0.000 claims abstract description 296
- 102100036537 von Willebrand factor Human genes 0.000 claims abstract description 164
- 108010047303 von Willebrand Factor Proteins 0.000 claims abstract description 155
- 229960001134 von willebrand factor Drugs 0.000 claims abstract description 149
- 241000282414 Homo sapiens Species 0.000 claims abstract description 57
- 201000007023 Thrombotic Thrombocytopenic Purpura Diseases 0.000 claims abstract description 10
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims description 118
- 238000011282 treatment Methods 0.000 claims description 100
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 99
- 230000000694 effects Effects 0.000 claims description 96
- 108091005670 ADAMTS13 Proteins 0.000 claims description 41
- 150000001413 amino acids Chemical class 0.000 claims description 25
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 17
- 238000004458 analytical method Methods 0.000 claims description 12
- 230000008859 change Effects 0.000 claims description 5
- 238000002648 combination therapy Methods 0.000 claims description 4
- 230000001506 immunosuppresive effect Effects 0.000 claims description 3
- 102100032290 A disintegrin and metalloproteinase with thrombospondin motifs 13 Human genes 0.000 claims 5
- 201000010099 disease Diseases 0.000 abstract description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 53
- 230000004044 response Effects 0.000 abstract description 32
- 230000007423 decrease Effects 0.000 abstract description 9
- 101000795753 Homo sapiens mRNA decay activator protein ZFP36 Proteins 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 description 119
- 238000009472 formulation Methods 0.000 description 106
- 108010023376 caplacizumab Proteins 0.000 description 104
- 210000001772 blood platelet Anatomy 0.000 description 84
- 210000002381 plasma Anatomy 0.000 description 51
- 230000027455 binding Effects 0.000 description 46
- 239000000427 antigen Substances 0.000 description 43
- 102000036639 antigens Human genes 0.000 description 43
- 108091007433 antigens Proteins 0.000 description 43
- 229940068196 placebo Drugs 0.000 description 39
- 239000000902 placebo Substances 0.000 description 39
- 229950002176 caplacizumab Drugs 0.000 description 37
- 102000043853 ADAMTS13 Human genes 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 35
- 230000001154 acute effect Effects 0.000 description 30
- 239000012634 fragment Substances 0.000 description 30
- 235000001014 amino acid Nutrition 0.000 description 27
- 230000005713 exacerbation Effects 0.000 description 25
- 108090000623 proteins and genes Proteins 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 22
- 239000003814 drug Substances 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 238000006467 substitution reaction Methods 0.000 description 21
- 238000003556 assay Methods 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- 238000011084 recovery Methods 0.000 description 17
- 229940079593 drug Drugs 0.000 description 16
- 230000003993 interaction Effects 0.000 description 16
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- 230000009467 reduction Effects 0.000 description 15
- -1 rituximab) Substances 0.000 description 15
- 238000003860 storage Methods 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 239000000872 buffer Substances 0.000 description 14
- 238000004108 freeze drying Methods 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 208000024891 symptom Diseases 0.000 description 13
- 208000032843 Hemorrhage Diseases 0.000 description 12
- 239000000546 pharmaceutical excipient Substances 0.000 description 12
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 11
- 125000000539 amino acid group Chemical group 0.000 description 11
- 230000008901 benefit Effects 0.000 description 11
- 239000003599 detergent Substances 0.000 description 11
- 235000000346 sugar Nutrition 0.000 description 11
- 208000034158 bleeding Diseases 0.000 description 10
- 230000000740 bleeding effect Effects 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 10
- 238000010494 dissociation reaction Methods 0.000 description 10
- 230000005593 dissociations Effects 0.000 description 10
- 230000007017 scission Effects 0.000 description 10
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 9
- 229930006000 Sucrose Natural products 0.000 description 9
- 239000011230 binding agent Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000007979 citrate buffer Substances 0.000 description 9
- 230000034994 death Effects 0.000 description 9
- 231100000517 death Toxicity 0.000 description 9
- 238000007710 freezing Methods 0.000 description 9
- 230000008014 freezing Effects 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000005720 sucrose Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 8
- 230000002411 adverse Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000001976 improved effect Effects 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 8
- 229920000053 polysorbate 80 Polymers 0.000 description 8
- 239000003755 preservative agent Substances 0.000 description 8
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 7
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 7
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 7
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 7
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 238000007920 subcutaneous administration Methods 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- 229920000089 Cyclic olefin copolymer Polymers 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000004001 molecular interaction Effects 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- 229920003023 plastic Polymers 0.000 description 6
- 229920005862 polyol Polymers 0.000 description 6
- 150000003077 polyols Chemical class 0.000 description 6
- 238000001694 spray drying Methods 0.000 description 6
- 150000008163 sugars Chemical class 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 206010043554 thrombocytopenia Diseases 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 208000007587 Transfusion-Related Acute Lung Injury Diseases 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 102000025171 antigen binding proteins Human genes 0.000 description 5
- 108091000831 antigen binding proteins Proteins 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 239000012131 assay buffer Substances 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 229940072221 immunoglobulins Drugs 0.000 description 5
- 230000002035 prolonged effect Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000009261 transgenic effect 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
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000011088 calibration curve Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 229920001971 elastomer Polymers 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 230000000302 ischemic effect Effects 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010002383 Angina Pectoris Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 3
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 3
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- 101800000620 Disintegrin-like Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 101000782195 Homo sapiens von Willebrand factor Proteins 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 3
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 208000007718 Stable Angina Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 108060008245 Thrombospondin Proteins 0.000 description 3
- 102000002938 Thrombospondin Human genes 0.000 description 3
- 208000007814 Unstable Angina Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 238000011461 current therapy Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 208000031169 hemorrhagic disease Diseases 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 150000005846 sugar alcohols Chemical class 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- DIHXSRXTECMMJY-MURFETPASA-N 2-[dimethyl-[(9z,12z)-octadeca-9,12-dienyl]azaniumyl]acetate Chemical group CCCCC\C=C/C\C=C/CCCCCCCC[N+](C)(C)CC([O-])=O DIHXSRXTECMMJY-MURFETPASA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 102100026735 Coagulation factor VIII Human genes 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 208000022774 Congenital thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 108010054218 Factor VIII Proteins 0.000 description 2
- 102000001690 Factor VIII Human genes 0.000 description 2
- 206010016803 Fluid overload Diseases 0.000 description 2
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 2
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- 206010062713 Haemorrhagic diathesis Diseases 0.000 description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000035888 Immune-mediated thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 101800001904 NT-proBNP Proteins 0.000 description 2
- 102400001263 NT-proBNP Human genes 0.000 description 2
- 102100036836 Natriuretic peptides B Human genes 0.000 description 2
- 101710187802 Natriuretic peptides B Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 206010062546 Thrombosis in device Diseases 0.000 description 2
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000004886 acquired thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 230000002785 anti-thrombosis Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 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
- 210000001185 bone marrow Anatomy 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 229960000301 factor viii Drugs 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 2
- 230000007106 neurocognition Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 229940020573 plavix Drugs 0.000 description 2
- 201000003144 pneumothorax Diseases 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229940107685 reopro Drugs 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000013517 stratification Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 230000001732 thrombotic effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- LMVGXBRDRZOPHA-UHFFFAOYSA-N 2-[dimethyl-[3-(16-methylheptadecanoylamino)propyl]azaniumyl]acetate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC([O-])=O LMVGXBRDRZOPHA-UHFFFAOYSA-N 0.000 description 1
- TYIOVYZMKITKRO-UHFFFAOYSA-N 2-[hexadecyl(dimethyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)CC([O-])=O TYIOVYZMKITKRO-UHFFFAOYSA-N 0.000 description 1
- SNQVCAOGQHOSEN-UHFFFAOYSA-N 2-[methyl(octadecyl)amino]acetic acid Chemical compound CCCCCCCCCCCCCCCCCCN(C)CC(O)=O SNQVCAOGQHOSEN-UHFFFAOYSA-N 0.000 description 1
- DIROHOMJLWMERM-UHFFFAOYSA-N 3-[dimethyl(octadecyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O DIROHOMJLWMERM-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 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
- 241000228212 Aspergillus Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 102000001187 Collagen Type III Human genes 0.000 description 1
- 108010069502 Collagen Type III Proteins 0.000 description 1
- 102000002734 Collagen Type VI Human genes 0.000 description 1
- 108010043741 Collagen Type VI Proteins 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 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
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- UNXHWFMMPAWVPI-QWWZWVQMSA-N D-threitol Chemical compound OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- 206010014522 Embolism venous Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 206010022678 Intestinal infections Diseases 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- RGHNJXZEOKUKBD-KLVWXMOXSA-N L-gluconic acid Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O RGHNJXZEOKUKBD-KLVWXMOXSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-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
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 206010027527 Microangiopathic haemolytic anaemia Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- 229920002651 Polysorbate 85 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108010081391 Ristocetin Proteins 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000036064 Surgical Blood Loss Diseases 0.000 description 1
- 244000125380 Terminalia tomentosa Species 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102000013394 Troponin I Human genes 0.000 description 1
- 108010065729 Troponin I Proteins 0.000 description 1
- 102000004987 Troponin T Human genes 0.000 description 1
- 108090001108 Troponin T Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000011360 adjunctive therapy Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 239000007864 aqueous solution Substances 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
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000009141 biological interaction Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 238000009640 blood culture Methods 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000000533 capillary isoelectric focusing Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- BGTFCAQCKWKTRL-YDEUACAXSA-N chembl1095986 Chemical compound C1[C@@H](N)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]([C@H]1C(N[C@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(C(=C(O)C=4)C)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@@H](C(=O)N3)[C@H](O)C=3C=CC(O4)=CC=3)C(=O)N1)C(O)=O)=O)C(C=C1)=CC=C1OC1=C(O[C@@H]3[C@H]([C@H](O)[C@@H](O)[C@H](CO[C@@H]5[C@H]([C@@H](O)[C@H](O)[C@@H](C)O5)O)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@H](O)[C@@H](CO)O3)O)C4=CC2=C1 BGTFCAQCKWKTRL-YDEUACAXSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 108060002894 fibrillar collagen Proteins 0.000 description 1
- 102000013373 fibrillar collagen Human genes 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 238000007478 fluorogenic assay Methods 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000004023 fresh frozen plasma Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 231100001156 grade 3 toxicity Toxicity 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 231100000206 health hazard Toxicity 0.000 description 1
- 125000001976 hemiacetal group Chemical group 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- NZXVYLJKFYSEPO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-16-methylheptadecanamide Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)NCCCN(C)C NZXVYLJKFYSEPO-UHFFFAOYSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 229940113171 polysorbate 85 Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 229950004257 ristocetin Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000009120 supportive therapy Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940104261 taurate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000003582 thrombocytopenic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000004043 venous thromboembolism Diseases 0.000 description 1
- 238000010865 video microscopy Methods 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940019333 vitamin k antagonists Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- 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
- C07K16/36—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- C07K2317/50—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
- C07K2317/50—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
- C07K2317/567—Framework region [FR]
-
- 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
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Priority Applications (45)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL2013007A NL2013007B1 (en) | 2014-06-16 | 2014-06-16 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof. |
| PL18153676T PL3332800T3 (pl) | 2014-06-16 | 2015-06-16 | Pojedyncze domeny zmienne immunoglobuliny do stosowania w sposobach leczenia TTP |
| PT181536715T PT3366305T (pt) | 2014-06-16 | 2015-06-16 | Métodos de tratamento de ttp com domínios variáveis únicos de imunoglobulina e seus usos |
| EP22172948.6A EP4059513A1 (en) | 2014-06-16 | 2015-06-16 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| PL18153673.1T PL3335723T3 (pl) | 2014-06-16 | 2015-06-16 | Pojedyncze domeny zmienne immunoglobuliny do zastosowania w sposobach leczenia TTP |
| ES18153676T ES2831865T3 (es) | 2014-06-16 | 2015-06-16 | Dominios variables únicos de inmunoglobulina para su uso en métodos de tratamiento de TTP |
| RU2019131713A RU2807602C2 (ru) | 2014-06-16 | 2015-06-16 | Способы лечения ттп иммуноглобулиновыми одиночными вариабельными доменами и их применение |
| US15/319,467 US10858445B2 (en) | 2014-06-16 | 2015-06-16 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof |
| ES18153674T ES2924199T3 (es) | 2014-06-16 | 2015-06-16 | Dominios variables individuales de inmunoglobulina para el uso en métodos para tratar TTP |
| PL18153674.9T PL3335724T3 (pl) | 2014-06-16 | 2015-06-16 | Pojedyncze domeny zmienne immunoglobuliny do zastosowania w sposobach leczenia TTP |
| PT181536731T PT3335723T (pt) | 2014-06-16 | 2015-06-16 | Domínios variáveis únicos de imunoglobulina para utilização em métodos de tratamento da ptt |
| ES18153671T ES2843642T3 (es) | 2014-06-16 | 2015-06-16 | Métodos de tratamiento de TTP con dominios variables únicos de inmunoglobulina y usos de los mismos |
| EP18153674.9A EP3335724B1 (en) | 2014-06-16 | 2015-06-16 | Immunoglobulin single variable domains for use in methods of treating ttp |
| KR1020177001152A KR102403388B1 (ko) | 2014-06-16 | 2015-06-16 | 면역글로불린 단일 가변 도메인을 이용한 ttp의 치료 방법 및 그의 용도 |
| SG11201610488QA SG11201610488QA (en) | 2014-06-16 | 2015-06-16 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| CA2952103A CA2952103A1 (en) | 2014-06-16 | 2015-06-16 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| ES18153673T ES2915473T3 (es) | 2014-06-16 | 2015-06-16 | Dominios variables únicos de inmunoglobulina para su uso en métodos de tratamiento de TTP |
| EP18153676.4A EP3332800B1 (en) | 2014-06-16 | 2015-06-16 | Immunoglobulin single variable domains for use in methods of treating ttp |
| KR1020227012546A KR102568585B1 (ko) | 2014-06-16 | 2015-06-16 | 면역글로불린 단일 가변 도메인을 이용한 ttp의 치료 방법 및 그의 용도 |
| SG10201811109PA SG10201811109PA (en) | 2014-06-16 | 2015-06-16 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| PL18153671T PL3366305T3 (pl) | 2014-06-16 | 2015-06-16 | Sposoby leczenia ttp za pomocą pojedyńczych immunoglobulinowych domen zmiennych i ich zastosowania |
| PT181536764T PT3332800T (pt) | 2014-06-16 | 2015-06-16 | Domínios variáveis únicos de imunoglobulina para utilização em métodos de tratamento da ptt |
| ES15729829T ES2881331T3 (es) | 2014-06-16 | 2015-06-16 | Dominios variables únicos de inmunoglobulina para su uso en el tratamiento de TTP |
| PCT/EP2015/063493 WO2015193326A1 (en) | 2014-06-16 | 2015-06-16 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| PT181536749T PT3335724T (pt) | 2014-06-16 | 2015-06-16 | Domínios variáveis únicos de imunoglobulina para utilização no tratamento da ptt |
| EP18153671.5A EP3366305B1 (en) | 2014-06-16 | 2015-06-16 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| JP2016573549A JP6688746B2 (ja) | 2014-06-16 | 2015-06-16 | 免疫グロブリン単一可変ドメインでｔｔｐを処置する方法、およびその使用 |
| EP15729829.0A EP3154569B1 (en) | 2014-06-16 | 2015-06-16 | Immunoglobulin single variable domains for use in treating ttp |
| CN201580040020.4A CN106559985A (zh) | 2014-06-16 | 2015-06-16 | 用免疫球蛋白单可变结构域治疗ttp的方法及其用途 |
| RU2017100077A RU2704444C2 (ru) | 2014-06-16 | 2015-06-16 | Способы лечения ттп иммуноглобулиновыми одиночными вариабельными доменами и их применение |
| PT157298290T PT3154569T (pt) | 2014-06-16 | 2015-06-16 | Domínios variáveis únicos de imunoglobulina para utilização no tratamento da ptt |
| PL15729829T PL3154569T3 (pl) | 2014-06-16 | 2015-06-16 | Pojedyncze domeny zmienne immunoglobuliny do zastosowania w leczeniu TTP |
| EP18153673.1A EP3335723B1 (en) | 2014-06-16 | 2015-06-16 | Immunoglobulin single variable domains for use in methods of treating ttp |
| AU2015276237A AU2015276237B2 (en) | 2014-06-16 | 2015-06-16 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof |
| IL249540A IL249540B (en) | 2014-06-16 | 2016-12-13 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| US15/880,978 US12269893B2 (en) | 2014-06-16 | 2018-01-26 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof |
| US15/881,003 US10919980B2 (en) | 2014-06-16 | 2018-01-26 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof |
| US15/880,870 US20180155440A1 (en) | 2014-06-16 | 2018-01-26 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| US15/881,055 US20180155443A1 (en) | 2014-06-16 | 2018-01-26 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| HK18115789.3A HK1256731B (en) | 2014-06-16 | 2018-12-10 | Immunoglobulin single variable domains for use in methods of treating ttp |
| HK18115787.5A HK1256730B (en) | 2014-06-16 | 2018-12-10 | Immunoglobulin single variable domains for use in methods of treating ttp |
| HK19100857.1A HK1258508B (en) | 2014-06-16 | 2019-01-17 | Methods of treating ttp with immunoglobulin single variable domains and uses thereof |
| JP2020014229A JP7105260B2 (ja) | 2014-06-16 | 2020-01-30 | 免疫グロブリン単一可変ドメインでｔｔｐを処置する方法、およびその使用 |
| AU2021202747A AU2021202747B2 (en) | 2014-06-16 | 2021-05-03 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof |
| JP2022110921A JP2022160431A (ja) | 2014-06-16 | 2022-07-11 | 免疫グロブリン単一可変ドメインでｔｔｐを処置する方法、およびその使用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL2013007A NL2013007B1 (en) | 2014-06-16 | 2014-06-16 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL2013007B1 true NL2013007B1 (en) | 2016-07-05 |
Family
ID=51541255
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL2013007A NL2013007B1 (en) | 2014-06-16 | 2014-06-16 | Methods of treating TTP with immunoglobulin single variable domains and uses thereof. |
Country Status (15)
| Country | Link |
|---|---|
| US (5) | US10858445B2 (enExample) |
| EP (6) | EP3366305B1 (enExample) |
| JP (3) | JP6688746B2 (enExample) |
| KR (2) | KR102403388B1 (enExample) |
| CN (1) | CN106559985A (enExample) |
| AU (2) | AU2015276237B2 (enExample) |
| CA (1) | CA2952103A1 (enExample) |
| ES (5) | ES2881331T3 (enExample) |
| IL (1) | IL249540B (enExample) |
| NL (1) | NL2013007B1 (enExample) |
| PL (5) | PL3332800T3 (enExample) |
| PT (5) | PT3366305T (enExample) |
| RU (1) | RU2704444C2 (enExample) |
| SG (2) | SG10201811109PA (enExample) |
| WO (1) | WO2015193326A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL2013007B1 (en) | 2014-06-16 | 2016-07-05 | Ablynx Nv | Methods of treating TTP with immunoglobulin single variable domains and uses thereof. |
| CN107340225B (zh) * | 2017-07-13 | 2019-07-05 | 徐州医科大学 | 一种基于流式细胞术检测血小板受体GPIba胞外段酶切的方法 |
| AU2019217584B2 (en) * | 2018-02-06 | 2025-08-14 | Ablynx Nv | Methods of treating initial episode of TTP with immunoglobulin single variable domains |
| IL302984A (en) * | 2020-11-18 | 2023-07-01 | Green Cross Corp | Adamts13 variant having increased escaping rate or activity against autoantibody |
| EP4402165A1 (en) | 2021-09-17 | 2024-07-24 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Synthetic humanized llama nanobody library and use thereof to identify sars-cov-2 neutralizing antibodies |
| WO2023108095A1 (en) * | 2021-12-10 | 2023-06-15 | Emory University | Polypeptides that bind to von willebrand factor (vwf) al domain or an autoinhibitory module, variants, and uses thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006122825A2 (en) * | 2005-05-20 | 2006-11-23 | Ablynx Nv | Single domain vhh antibodies against von willebrand factor |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB335768A (en) | 1929-10-24 | 1930-10-02 | Jacoviac Maurice | Improvements in protecting devices for gramophone disc records |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5043429B1 (en) | 1987-05-01 | 1997-10-14 | Scripps Research Inst | Protein fragments containing factor VIII binding domain of von willebrand factor |
| JP2919890B2 (ja) | 1988-11-11 | 1999-07-19 | メディカル リサーチ カウンスル | 単一ドメインリガンド、そのリガンドからなる受容体、その製造方法、ならびにそのリガンドおよび受容体の使用 |
| DE69330523T4 (de) | 1992-08-21 | 2012-08-23 | Vrije Universiteit Brussel | Immunoglobuline ohne leichte ketten |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US6329516B1 (en) | 1997-04-28 | 2001-12-11 | Fmc Corporation | Lepidopteran GABA-gated chloride channels |
| WO2000046383A2 (en) | 1999-02-05 | 2000-08-10 | Rijksuniversiteit Leiden | Method of modulating metabolite biosynthesis in recombinant cells |
| EP1198572A2 (en) | 1999-08-02 | 2002-04-24 | Keygene N.V. | Method for generating cgmmv resistant plants, genetic constructs, and obtained cgmmv-resistant plants |
| US20060073141A1 (en) | 2001-06-28 | 2006-04-06 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| EP1527346B1 (en) | 2002-08-07 | 2011-06-08 | Ablynx N.V. | Modulation of platelet adhesion based on the surface exposed beta-switch loop of platelet glycoprotein ib-alpha |
| WO2004037999A2 (en) | 2002-10-23 | 2004-05-06 | Ludwig Institute For Cancer Research | A34 and a33-like 3 dna, proteins, antibodies thereto and methods of treatment using same |
| BRPI0406694B8 (pt) | 2003-01-10 | 2021-05-25 | Ablynx Nv | polipeptídios terapêutico, seus homólogos, seus fragmentos, que são usados nas modulações da agregação plaquetária |
| RU2524129C2 (ru) | 2003-01-10 | 2014-07-27 | Аблинкс Н.В. | Терапевтические полипептиды, их гомологи, их фрагменты и их применение для модуляции агрегации, опосредованной тромбоцитами |
| US7461263B2 (en) | 2003-01-23 | 2008-12-02 | Unspam, Llc. | Method and apparatus for a non-revealing do-not-contact list system |
| CA2535550A1 (en) | 2003-08-12 | 2005-03-03 | William M. Yarbrough | Treatment for acne vulgaris and method of use |
| US7270976B2 (en) * | 2004-07-19 | 2007-09-18 | American Diagnostica, Inc. | Methods for measuring ADAMTS13 activity and protein on platelets and in plasma |
| US7563443B2 (en) * | 2004-09-17 | 2009-07-21 | Domantis Limited | Monovalent anti-CD40L antibody polypeptides and compositions thereof |
| RU2007117752A (ru) | 2004-10-13 | 2008-11-20 | Аблинкс Н.В. (Be) | Нанотела (nanobodies тм) против бета-амилоида и полипептидов, содержащих бета-амилоид, для лечения нейродегенеративных заболеваний, таких как болезнь альцгеймера |
| ATE473446T1 (de) | 2005-01-14 | 2010-07-15 | Ablynx Nv | Verfahren und testvorrichtungen zur unterscheidung verschiedener formen von krankheiten und leiden, die durch thrombocytopenia und/oder durch spontane interaktionen zwischen dem von-willebrand-faktor und plättchen gekennzeichnet sind |
| AU2007285695B2 (en) | 2006-08-18 | 2012-05-24 | Ablynx N.V. | Amino acid sequences directed against IL-6R and polypeptides comprising the same for the treatment of diseases and disorders associated with IL-6-mediated signalling |
| JP2010518839A (ja) | 2007-02-21 | 2010-06-03 | アブリンクス エン．ヴェー． | 血管内皮増殖因子に指向性を有するアミノ酸配列、及び過度の及び／もしくは病的な血管形成又は血管新生を特徴とする症状及び疾患を治療するためにこれを含むポリペプチド |
| WO2008142164A2 (en) | 2007-05-24 | 2008-11-27 | Ablynx N.V. | Amino acid sequences directed against rank-l and polypeptides comprising the same for the treatment of bone diseases and disorders |
| AU2009227055A1 (en) | 2008-03-21 | 2009-09-24 | Ablynx Nv | Von Willebrand Factor specific binders and methods of use therefor |
| BRPI0919979A2 (pt) | 2008-10-29 | 2015-12-15 | Wyeth Llc | formulações de moléculas de ligação de antígeno de domínio único |
| CA2739352C (en) | 2008-10-29 | 2021-07-13 | Wyeth Llc | Methods for purification of single domain antigen binding molecules |
| WO2011067160A1 (en) | 2009-12-01 | 2011-06-09 | Ablynx Nv | Von willebrand factor specific binding agents and uses thereof |
| MX362591B (es) * | 2010-11-05 | 2019-01-25 | Novartis Ag | Uso de antagonistas de il-17. |
| AU2012267458A1 (en) | 2011-06-10 | 2014-01-09 | Baxalta GmbH | Treatment of coagulation disease by administration of recombinant VWF |
| KR102162413B1 (ko) | 2011-08-17 | 2020-10-07 | 글락소 그룹 리미티드 | 변형된 단백질 및 펩티드 |
| NL2013007B1 (en) | 2014-06-16 | 2016-07-05 | Ablynx Nv | Methods of treating TTP with immunoglobulin single variable domains and uses thereof. |
| AU2019217584B2 (en) | 2018-02-06 | 2025-08-14 | Ablynx Nv | Methods of treating initial episode of TTP with immunoglobulin single variable domains |
-
2014
- 2014-06-16 NL NL2013007A patent/NL2013007B1/en active
-
2015
- 2015-06-16 RU RU2017100077A patent/RU2704444C2/ru active
- 2015-06-16 US US15/319,467 patent/US10858445B2/en active Active
- 2015-06-16 EP EP18153671.5A patent/EP3366305B1/en active Active
- 2015-06-16 EP EP18153676.4A patent/EP3332800B1/en active Active
- 2015-06-16 CA CA2952103A patent/CA2952103A1/en not_active Abandoned
- 2015-06-16 PL PL18153676T patent/PL3332800T3/pl unknown
- 2015-06-16 PT PT181536715T patent/PT3366305T/pt unknown
- 2015-06-16 JP JP2016573549A patent/JP6688746B2/ja active Active
- 2015-06-16 PT PT181536764T patent/PT3332800T/pt unknown
- 2015-06-16 ES ES15729829T patent/ES2881331T3/es active Active
- 2015-06-16 PT PT157298290T patent/PT3154569T/pt unknown
- 2015-06-16 KR KR1020177001152A patent/KR102403388B1/ko active Active
- 2015-06-16 SG SG10201811109PA patent/SG10201811109PA/en unknown
- 2015-06-16 KR KR1020227012546A patent/KR102568585B1/ko active Active
- 2015-06-16 WO PCT/EP2015/063493 patent/WO2015193326A1/en not_active Ceased
- 2015-06-16 PL PL18153671T patent/PL3366305T3/pl unknown
- 2015-06-16 EP EP22172948.6A patent/EP4059513A1/en not_active Withdrawn
- 2015-06-16 ES ES18153671T patent/ES2843642T3/es active Active
- 2015-06-16 ES ES18153674T patent/ES2924199T3/es active Active
- 2015-06-16 SG SG11201610488QA patent/SG11201610488QA/en unknown
- 2015-06-16 PT PT181536731T patent/PT3335723T/pt unknown
- 2015-06-16 ES ES18153673T patent/ES2915473T3/es active Active
- 2015-06-16 PL PL18153674.9T patent/PL3335724T3/pl unknown
- 2015-06-16 PL PL15729829T patent/PL3154569T3/pl unknown
- 2015-06-16 PL PL18153673.1T patent/PL3335723T3/pl unknown
- 2015-06-16 EP EP18153673.1A patent/EP3335723B1/en active Active
- 2015-06-16 AU AU2015276237A patent/AU2015276237B2/en active Active
- 2015-06-16 EP EP15729829.0A patent/EP3154569B1/en active Active
- 2015-06-16 ES ES18153676T patent/ES2831865T3/es active Active
- 2015-06-16 PT PT181536749T patent/PT3335724T/pt unknown
- 2015-06-16 EP EP18153674.9A patent/EP3335724B1/en active Active
- 2015-06-16 CN CN201580040020.4A patent/CN106559985A/zh active Pending
-
2016
- 2016-12-13 IL IL249540A patent/IL249540B/en unknown
-
2018
- 2018-01-26 US US15/881,055 patent/US20180155443A1/en not_active Abandoned
- 2018-01-26 US US15/881,003 patent/US10919980B2/en active Active
- 2018-01-26 US US15/880,870 patent/US20180155440A1/en not_active Abandoned
- 2018-01-26 US US15/880,978 patent/US12269893B2/en active Active
-
2020
- 2020-01-30 JP JP2020014229A patent/JP7105260B2/ja active Active
-
2021
- 2021-05-03 AU AU2021202747A patent/AU2021202747B2/en active Active
-
2022
- 2022-07-11 JP JP2022110921A patent/JP2022160431A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006122825A2 (en) * | 2005-05-20 | 2006-11-23 | Ablynx Nv | Single domain vhh antibodies against von willebrand factor |
Non-Patent Citations (4)
| Title |
|---|
| F. CALLEWAERT ET AL: "Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura", BLOOD, vol. 120, no. 17, 4 September 2012 (2012-09-04), pages 3603 - 3610, XP055109473, ISSN: 0006-4971, DOI: 10.1182/blood-2012-04-420943 * |
| FLORA PEYVANDI ET AL: "Nanobodies - Inspired by nature First results of the Phase II TITAN trial: anti-von Willebrand factor Nanobody as adjunctive treatment for patients with acquired thrombotic thrombocytopenic purpura", 28 July 2011 (2011-07-28), XP055163774, Retrieved from the Internet <URL:http://www.ablynx.com/wp-content/uploads/2011/07/Peyvandi_TITAN-study_final.pdf> [retrieved on 20150121] * |
| JOSEFIN-BEATE HOLZ: "The TITAN trial Assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura", TRANSFUSION AND APHERESIS SCIENCE, vol. 46, no. 3, 2012, pages 343 - 346, XP028422906, ISSN: 1473-0502, [retrieved on 20120319], DOI: 10.1016/J.TRANSCI.2012.03.027 * |
| KENT CHAPMAN ET AL: "Therapy for Thrombotic Thrombocytopenia Purpura: Past, Present, and Future", SEMINARS IN THROMBOSIS AND HEMOSTASIS, vol. 40, no. 01, 31 December 2013 (2013-12-31), pages 034 - 040, XP055163569, ISSN: 0094-6176, DOI: 10.1055/s-0033-1363165 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10919980B2 (en) | Methods of treating TTP with immunoglobulin single variable domains and uses thereof | |
| US11999797B2 (en) | Methods of treating initial episode of TTP with immunoglobulin single variable domains | |
| HK40078326A (en) | Methods of treating ttp with immunoglobulin single variable domains and uses thereof | |
| HK1256731B (en) | Immunoglobulin single variable domains for use in methods of treating ttp | |
| HK1258508B (en) | Methods of treating ttp with immunoglobulin single variable domains and uses thereof | |
| HK1256730B (en) | Immunoglobulin single variable domains for use in methods of treating ttp | |
| HK1255930A1 (en) | Immunoglobulin single variable domains for use in methods of treating ttp | |
| HK1255930B (en) | Immunoglobulin single variable domains for use in methods of treating ttp | |
| HK1236434B (en) | Immunoglobulin single variable domains for use in treating ttp |