NO315076B1 - Dimerpreparat av molekyl¶rvariant av apolipoprotein og fremgangsmåter for fremstilling og anvendelse derav, til fremstilling av et medikamentfor behandling av aterosklerose og kardiovaskul¶re sykdommer - Google Patents
Dimerpreparat av molekyl¶rvariant av apolipoprotein og fremgangsmåter for fremstilling og anvendelse derav, til fremstilling av et medikamentfor behandling av aterosklerose og kardiovaskul¶re sykdommer Download PDFInfo
- Publication number
- NO315076B1 NO315076B1 NO19932866A NO932866A NO315076B1 NO 315076 B1 NO315076 B1 NO 315076B1 NO 19932866 A NO19932866 A NO 19932866A NO 932866 A NO932866 A NO 932866A NO 315076 B1 NO315076 B1 NO 315076B1
- Authority
- NO
- Norway
- Prior art keywords
- apo
- dimer
- apolipoprotein
- milano
- preparation
- Prior art date
Links
- 102000007592 Apolipoproteins Human genes 0.000 title claims abstract description 44
- 108010071619 Apolipoproteins Proteins 0.000 title claims abstract description 44
- 201000001320 Atherosclerosis Diseases 0.000 title claims abstract description 12
- 208000024172 Cardiovascular disease Diseases 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 21
- 238000004519 manufacturing process Methods 0.000 title claims description 17
- 238000011282 treatment Methods 0.000 title claims description 14
- 238000000034 method Methods 0.000 title description 11
- 239000000539 dimer Substances 0.000 claims abstract description 63
- 239000000178 monomer Substances 0.000 claims abstract description 18
- 241000588724 Escherichia coli Species 0.000 claims abstract description 10
- 239000000969 carrier Substances 0.000 claims abstract description 10
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 4
- 239000000651 prodrug Substances 0.000 claims abstract description 4
- 229940002612 prodrug Drugs 0.000 claims abstract description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 238000003776 cleavage reaction Methods 0.000 claims description 12
- 230000007017 scission Effects 0.000 claims description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 11
- 235000019253 formic acid Nutrition 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 8
- 239000002502 liposome Substances 0.000 claims description 8
- 150000002632 lipids Chemical class 0.000 claims description 7
- 238000005516 engineering process Methods 0.000 claims description 6
- 108020001507 fusion proteins Proteins 0.000 claims description 6
- 102000037865 fusion proteins Human genes 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- 230000001580 bacterial effect Effects 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 230000002093 peripheral effect Effects 0.000 claims description 4
- 150000003904 phospholipids Chemical class 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 4
- 239000003524 antilipemic agent Substances 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 claims description 3
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 230000002425 cardiocirculatory effect Effects 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 238000007887 coronary angioplasty Methods 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- 230000003834 intracellular effect Effects 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 230000018338 positive regulation of fibrinolysis Effects 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 206010053648 Vascular occlusion Diseases 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- 208000021331 vascular occlusion disease Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 41
- 108010010234 HDL Lipoproteins Proteins 0.000 description 32
- 102000015779 HDL Lipoproteins Human genes 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 30
- 235000018102 proteins Nutrition 0.000 description 28
- 102000013566 Plasminogen Human genes 0.000 description 27
- 108010051456 Plasminogen Proteins 0.000 description 27
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 27
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 239000013612 plasmid Substances 0.000 description 21
- 239000000872 buffer Substances 0.000 description 19
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 18
- 239000012634 fragment Substances 0.000 description 18
- 229960004198 guanidine Drugs 0.000 description 17
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 17
- 230000001965 increasing effect Effects 0.000 description 17
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 14
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 14
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 14
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 14
- 229940012957 plasmin Drugs 0.000 description 14
- 229960005356 urokinase Drugs 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 229960000187 tissue plasminogen activator Drugs 0.000 description 13
- 108010053070 Glutathione Disulfide Proteins 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000001994 activation Methods 0.000 description 12
- 239000000499 gel Substances 0.000 description 12
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 12
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 12
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 11
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 11
- 230000003480 fibrinolytic effect Effects 0.000 description 11
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 11
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229960003180 glutathione Drugs 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 108010073385 Fibrin Proteins 0.000 description 9
- 102000009123 Fibrin Human genes 0.000 description 9
- 229950003499 fibrin Drugs 0.000 description 9
- 239000003527 fibrinolytic agent Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 238000011993 High Performance Size Exclusion Chromatography Methods 0.000 description 8
- 102000004895 Lipoproteins Human genes 0.000 description 8
- 108090001030 Lipoproteins Proteins 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 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 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000001802 infusion Methods 0.000 description 7
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 229930027917 kanamycin Natural products 0.000 description 6
- 229960000318 kanamycin Drugs 0.000 description 6
- 229930182823 kanamycin A Natural products 0.000 description 6
- 230000003902 lesion Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000002211 ultraviolet spectrum Methods 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 4
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 4
- ZEFNOZRLAWVAQF-UHFFFAOYSA-N Dinitolmide Chemical compound CC1=C(C(N)=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O ZEFNOZRLAWVAQF-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 239000006391 Luria-Bertani Medium Substances 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 239000003593 chromogenic compound Substances 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 229960004441 tyrosine Drugs 0.000 description 4
- 235000002374 tyrosine Nutrition 0.000 description 4
- -1 0.01% Naa-EDTA Chemical compound 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 108010004103 Chylomicrons Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 3
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000001142 circular dichroism spectrum Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 230000033885 plasminogen activation Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102000006410 Apoproteins Human genes 0.000 description 2
- 108010083590 Apoproteins Proteins 0.000 description 2
- 200000000007 Arterial disease Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102000014190 Phosphatidylcholine-sterol O-acyltransferase Human genes 0.000 description 2
- 108010011964 Phosphatidylcholine-sterol O-acyltransferase Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 239000012506 Sephacryl® Substances 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 102000002933 Thioredoxin Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000003024 amidolytic effect Effects 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000002518 antifoaming agent Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 230000000923 atherogenic effect Effects 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 108010073651 fibrinmonomer Proteins 0.000 description 2
- 230000020764 fibrinolysis Effects 0.000 description 2
- 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 2
- 238000005194 fractionation Methods 0.000 description 2
- 238000001879 gelation Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960000344 thiamine hydrochloride Drugs 0.000 description 2
- 235000019190 thiamine hydrochloride Nutrition 0.000 description 2
- 239000011747 thiamine hydrochloride Substances 0.000 description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 2
- 108060008226 thioredoxin Proteins 0.000 description 2
- 229940094937 thioredoxin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 239000012137 tryptone Substances 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- CAJXYXPLLJDEOB-SLFFLAALSA-N (2s)-6-amino-2-[[(2s)-2-[[(2r)-2-amino-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-n-(4-nitrophenyl)hexanamide Chemical compound CC(C)[C@@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 CAJXYXPLLJDEOB-SLFFLAALSA-N 0.000 description 1
- DGYWXYFLXYIOCP-KBPBESRZSA-N (2s)-n-[2-[[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]amino]-2-oxoethyl]-5-oxopyrrolidine-2-carboxamide Chemical compound N([C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)C(=O)CNC(=O)[C@@H]1CCC(=O)N1 DGYWXYFLXYIOCP-KBPBESRZSA-N 0.000 description 1
- 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
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- 108010007858 5-oxo-prolyl-glycyl-arginine-4-nitroanilide Proteins 0.000 description 1
- 101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- UKGGPJNBONZZCM-WDSKDSINSA-N Asp-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O UKGGPJNBONZZCM-WDSKDSINSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 101100402795 Caenorhabditis elegans mtl-1 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 description 1
- 241000252095 Congridae Species 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 1
- 241000702374 Enterobacteria phage fd Species 0.000 description 1
- 101710121417 Envelope glycoprotein Proteins 0.000 description 1
- 101710204837 Envelope small membrane protein Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 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 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 101710088839 Replication initiation protein Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 101710100170 Unknown protein Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 1
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 1
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 101150042295 arfA gene Proteins 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 239000007478 blood agar base Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- FAPWYRCQGJNNSJ-CTWWJBIBSA-L calcium;3-[[(2s)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoate Chemical compound [Ca+2].OCC(C)(C)[C@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-CTWWJBIBSA-L 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 238000000978 circular dichroism spectroscopy Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 239000010200 folin Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000002565 heparin fraction Substances 0.000 description 1
- 239000002634 heparin fragment Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000001696 ion exchange chromatographie Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000013038 irreversible inhibitor Substances 0.000 description 1
- 238000002093 isoelectric focusing polyacrylamide gel electrophoresis Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000004576 lipid-binding Effects 0.000 description 1
- 230000008604 lipoprotein metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229910000357 manganese(II) sulfate Inorganic materials 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 101150079876 mcrB gene Proteins 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 101150087557 omcB gene Proteins 0.000 description 1
- 101150115693 ompA gene Proteins 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 101150059159 proA2 gene Proteins 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 230000004141 reverse cholesterol transport Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000005454 tryptophanyl group Chemical group 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000011686 zinc sulphate Substances 0.000 description 1
- 235000009529 zinc sulphate Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/775—Apolipopeptides
-
- 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Marine Sciences & Fisheries (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9103701A SE9103701D0 (sv) | 1991-12-13 | 1991-12-13 | Apolipoprotein |
| PCT/SE1992/000858 WO1993012143A1 (en) | 1991-12-13 | 1992-12-11 | Dimer of molecular variant of apolipoprotein and processes for the production thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO932866L NO932866L (no) | 1993-08-12 |
| NO932866D0 NO932866D0 (no) | 1993-08-12 |
| NO315076B1 true NO315076B1 (no) | 2003-07-07 |
Family
ID=20384608
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19932866A NO315076B1 (no) | 1991-12-13 | 1993-08-12 | Dimerpreparat av molekyl¶rvariant av apolipoprotein og fremgangsmåter for fremstilling og anvendelse derav, til fremstilling av et medikamentfor behandling av aterosklerose og kardiovaskul¶re sykdommer |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US5876968A (hu) |
| EP (1) | EP0571602B1 (hu) |
| JP (1) | JPH07502892A (hu) |
| AT (1) | ATE242269T1 (hu) |
| AU (2) | AU3175593A (hu) |
| BG (1) | BG61451B1 (hu) |
| BR (1) | BR9205640A (hu) |
| CA (1) | CA2103996C (hu) |
| CZ (1) | CZ289879B6 (hu) |
| DE (1) | DE69233092T2 (hu) |
| DK (1) | DK0571602T3 (hu) |
| EE (1) | EE03058B1 (hu) |
| ES (1) | ES2199939T3 (hu) |
| FI (1) | FI115771B (hu) |
| HU (2) | HU217203B (hu) |
| IL (1) | IL103956A (hu) |
| MX (1) | MX9207224A (hu) |
| NO (1) | NO315076B1 (hu) |
| NZ (2) | NZ246223A (hu) |
| PL (3) | PL171907B1 (hu) |
| PT (1) | PT571602E (hu) |
| RO (1) | RO115636B1 (hu) |
| RU (1) | RU2134696C1 (hu) |
| SE (1) | SE9103701D0 (hu) |
| SG (1) | SG47453A1 (hu) |
| SK (1) | SK86893A3 (hu) |
| WO (1) | WO1993012143A1 (hu) |
| ZA (1) | ZA928989B (hu) |
Families Citing this family (91)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9103701D0 (sv) * | 1991-12-13 | 1991-12-13 | Kabi Pharmacia Ab | Apolipoprotein |
| SE9203753D0 (sv) * | 1992-12-11 | 1992-12-11 | Kabi Pharmacia Ab | Expression system for producing apolipoprotein ai-m |
| SE9500778D0 (sv) | 1995-03-03 | 1995-03-03 | Pharmacia Ab | Process for producing a protein |
| US6258596B1 (en) | 1995-05-22 | 2001-07-10 | Aventis Pharmaceuticals Products Inc. | Variants of apolipoprotein A-I |
| FR2734568B1 (fr) * | 1995-05-22 | 1997-06-20 | Rhone Poulenc Rorer Sa | Nouveaux variants de l'apolipoproteine |
| SE9603068D0 (sv) * | 1996-08-23 | 1996-08-23 | Pharmacia & Upjohn Ab | Process for purifying a protein |
| SE9603303D0 (sv) | 1996-09-11 | 1996-09-11 | Pharmacia & Upjohn Ab | Process for purifying a protein |
| SE9603304D0 (sv) | 1996-09-11 | 1996-09-11 | Pharmacia & Upjohn Ab | Process for purifying a compound |
| US6306433B1 (en) | 1997-08-12 | 2001-10-23 | Pharmacia Ab | Method of preparing pharmaceutical compositions |
| US20020064820A1 (en) * | 2000-03-13 | 2002-05-30 | Jean-Michel Dayer | Apo-A-I regulation of T-cell signaling |
| DK1290013T3 (da) * | 2000-04-21 | 2006-06-26 | Amgen Inc | Apo-A1/All-peptidderivater |
| BRPI0003386B8 (pt) * | 2000-08-08 | 2021-05-25 | Cristalia Produtos Quim Farmaceuticos Ltda | pró-droga homo ou heterodiméricas úteis no tratamento de doenças ou disfunções mediadas por fosfodiesterases; composições farmacêuticas contendo a pró-droga ou seus sais farmacêuticos aceitáveis; processo de obtenção destas pró-drogas |
| US6664230B1 (en) * | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| US8568766B2 (en) | 2000-08-24 | 2013-10-29 | Gattadahalli M. Anantharamaiah | Peptides and peptide mimetics to treat pathologies associated with eye disease |
| AU2002213843B2 (en) * | 2000-11-10 | 2008-02-07 | F. Hoffmann-La Roche Ltd. | Apolipoprotein analogues |
| US7217785B2 (en) | 2001-05-09 | 2007-05-15 | The Regents Of The University Of California | Cysteine-containing peptides having antioxidant properties |
| WO2003026492A2 (en) * | 2001-09-28 | 2003-04-03 | Esperion Therapeutics Inc. | Prevention and treatment of restenosis by local administration of drug |
| AU2002360489A1 (en) * | 2001-12-07 | 2003-06-23 | The Regents Of The University Of California | Treatment for age-related macular degeneration |
| US20030229062A1 (en) * | 2001-12-07 | 2003-12-11 | The Regents Of The University Of California | Treatments for age-related macular degeneration (AMD) |
| US7470659B2 (en) * | 2001-12-07 | 2008-12-30 | The Regents Of The University Of California | Methods to increase reverse cholesterol transport in the retinal pigment epithelium (RPE) and Bruch's membrane (BM) |
| US7223726B2 (en) * | 2002-01-14 | 2007-05-29 | The Regents Of The University Of California | Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same |
| US20100204103A1 (en) * | 2002-05-08 | 2010-08-12 | The Regents Of The University Of California | Helical synthetic peptides that stimulate cellular cholesterol efflux |
| US20040067873A1 (en) | 2002-05-17 | 2004-04-08 | Dasseux Jean-Louis H. | Method of treating dyslipidemic disorders |
| MXPA04011227A (es) * | 2002-05-17 | 2005-01-25 | Esperion Therapeutics Inc | Metodos y composiciones para el tratamiento de la reperfusion isquemica. |
| SE0302312D0 (sv) * | 2002-10-04 | 2003-08-27 | Forskarpatent I Syd Ab | Peptide-based passive immunization therapy for treatment of atherosclerosis |
| DE10324447A1 (de) | 2003-05-28 | 2004-12-30 | Scil Proteins Gmbh | Generierung künstlicher Bindungsproteine auf der Grundlage von Ubiquitin |
| PE20050438A1 (es) * | 2003-10-20 | 2005-06-14 | Esperion Therapeutics Inc | Formulas farmaceuticas, metodos y regimenes de dosificacion para el tratamiento y la prevencion de sindromes coronarios agudos |
| WO2005051413A2 (en) * | 2003-11-26 | 2005-06-09 | Novartis Ag | Disease associated genes |
| WO2005058938A2 (en) * | 2003-12-15 | 2005-06-30 | The Regents Of The University Of California | Helical synthetic peptides that stimulate cellular cholesterol efflux |
| EP1732383A4 (en) | 2004-04-06 | 2007-05-02 | Cedars Sinai Medical Center | PREVENTION AND TREATMENT OF VASCULAR DISEASES WITH RECOMBINANT ADENO ASSOCIATED VIRUS VECTORS THAT CODE APOLIPOPROTEIN A-I AND APOLIPOPROTEIN A-I MILANO |
| KR100560102B1 (ko) * | 2004-06-25 | 2006-03-13 | 한국생명공학연구원 | 프로아포리포단백질 a-ⅰ 변이체와, 이를 포함하는고지혈증 또는 동맥경화증 예방 및 치료제 |
| US9487575B2 (en) * | 2004-07-14 | 2016-11-08 | The Regents Of The University Of California | Compositions and methods for treatment of gynecologic cancers |
| US8206750B2 (en) | 2005-03-24 | 2012-06-26 | Cerenis Therapeutics Holding S.A. | Charged lipoprotein complexes and their uses |
| BRPI0610983A2 (pt) | 2005-04-29 | 2010-08-10 | Universirty Of California | peptìdeos e miméticos de peptìdeos para tratar patologias caracterizadas por uma resposta inflamatória |
| WO2007000924A1 (ja) * | 2005-06-28 | 2007-01-04 | Osaka University | プログラニュリン活性を抑制または促進する物質を含む医薬組成物、およびプログラニュリン活性を抑制または促進する物質のスクリーニング方法 |
| KR100719389B1 (ko) | 2005-10-18 | 2007-05-17 | 주식회사 녹십자 | 인간혈장으로부터 아포리포단백질 a-i을 분리 정제하는방법 |
| US20070254832A1 (en) * | 2006-02-17 | 2007-11-01 | Pressler Milton L | Methods for the treatment of macular degeneration and related eye conditions |
| WO2008021088A2 (en) | 2006-08-08 | 2008-02-21 | The Regents Of The University Of Californina | Salicylanilides enhance oral delivery of therapeutic peptides |
| US9637753B2 (en) * | 2006-08-10 | 2017-05-02 | Plantechno S.R.L. | In-plant production of oligomeric (comprising three or more units) forms of human Apo A-1 protein muteins |
| US8541236B2 (en) * | 2006-12-08 | 2013-09-24 | University Of Washington | Mutant apolipoprotein A-1 polypeptide with increased resistance to oxidation and reactive carbonyls |
| US9422363B2 (en) | 2007-08-28 | 2016-08-23 | Uab Research Foundation | Synthetic apolipoprotein E mimicking polypeptides and methods of use |
| WO2009032702A2 (en) | 2007-08-28 | 2009-03-12 | Uab Research Foundation | Synthetic apolipoprotein e mimicking polypeptides and methods of use |
| WO2009050266A2 (en) * | 2007-10-19 | 2009-04-23 | Pronota N.V. | Use of n-terminal and c-terminal proteomics technology to enhance protein therapeutics and diagnostics |
| KR20100100824A (ko) | 2007-10-23 | 2010-09-15 | 더 클리브랜드 클리닉 파운데이션 | 산화제 내성 아포지단백질 a-1 및 모방체 펩티드 |
| US8241861B1 (en) | 2008-07-08 | 2012-08-14 | Insilicos, Llc | Methods and compositions for diagnosis or prognosis of cardiovascular disease |
| CN111909020A (zh) | 2008-11-10 | 2020-11-10 | 阿布特斯生物制药公司 | 用于递送治疗剂的脂质和组合物 |
| US20120101148A1 (en) | 2009-01-29 | 2012-04-26 | Alnylam Pharmaceuticals, Inc. | lipid formulation |
| CA2754043A1 (en) | 2009-03-12 | 2010-09-16 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes |
| KR20240015723A (ko) | 2009-05-05 | 2024-02-05 | 알닐람 파마슈티칼스 인코포레이티드 | 지질 조성물 |
| CA2764609C (en) | 2009-06-10 | 2018-10-02 | Alnylam Pharmaceuticals, Inc. | Improved cationic lipid of formula i |
| WO2011020023A2 (en) | 2009-08-14 | 2011-02-17 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus |
| WO2011044545A2 (en) | 2009-10-09 | 2011-04-14 | Sigalov Alexander B | Methods and compositions for targeted imaging |
| US10894098B2 (en) | 2012-04-09 | 2021-01-19 | Signablok, Inc. | Methods and compositions for targeted imaging |
| US12419839B2 (en) | 2009-10-09 | 2025-09-23 | Signablok, Inc. | Methods and compositions for targeted delivery of protein fragments |
| AU2010328336B2 (en) | 2009-12-07 | 2017-03-02 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
| DK2379581T3 (da) * | 2009-12-14 | 2014-01-06 | Scil Proteins Gmbh | Fremgangsmåde til identifikation af hetero-multimerisk modificerede ubiquitinproteiner med evne til binding til ligander |
| WO2011075656A1 (en) | 2009-12-18 | 2011-06-23 | The University Of British Columbia | Methods and compositions for delivery of nucleic acids |
| US20130156845A1 (en) | 2010-04-29 | 2013-06-20 | Alnylam Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
| WO2011143362A1 (en) * | 2010-05-11 | 2011-11-17 | Esperion Therapeutics, Inc. | Dimeric oxidation-resistant apolipoprotein a1 variants |
| ES3053320T3 (en) | 2010-06-03 | 2026-01-21 | Alnylam Pharmaceuticals Inc | Biodegradable lipids for the delivery of active agents |
| WO2012016188A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
| WO2012016184A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
| US20130142760A1 (en) | 2010-08-18 | 2013-06-06 | Cedars-Sinai Medical Center | Atherosclerosis inhibition via modulation of monocyte-macrophage phenotype using apo a-i milano gene transfer |
| US9339513B2 (en) | 2010-11-09 | 2016-05-17 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes |
| EP3202760B1 (en) | 2011-01-11 | 2019-08-21 | Alnylam Pharmaceuticals, Inc. | Pegylated lipids and their use for drug delivery |
| CN103443123B (zh) | 2011-02-07 | 2020-05-29 | 塞勒尼斯医疗控股公司 | 脂蛋白复合物及其制备和用途 |
| WO2012172055A1 (en) | 2011-06-15 | 2012-12-20 | Scil Proteins Gmbh | Dimeric binding proteins based on modified ubiquitins |
| MX2014001920A (es) | 2011-08-25 | 2014-04-14 | Hoffmann La Roche | Proteina de fusion acortada de tetranectina-apolipoproteina a-i, una particula lipidica que la contiene, y usos de la misma. |
| JP6250543B2 (ja) | 2011-09-27 | 2017-12-20 | アルニラム・ファーマシューティカルズ・インコーポレーテッド | ジ脂肪族置換peg化脂質 |
| US9610324B2 (en) | 2012-07-11 | 2017-04-04 | Esperion Therapeutics, Inc. | Apolipoprotein mixtures |
| EP2853259A1 (en) | 2013-09-30 | 2015-04-01 | Université Pierre et Marie Curie (Paris 6) | Reconstituted high density lipoproteins composition and uses thereof |
| MX2016014306A (es) | 2014-05-02 | 2017-06-12 | Cerenis Therapeutics Holding Sa | Marcadores para terapia con lipoproteinas de alta densidad (hdl). |
| USRE50320E1 (en) | 2014-07-31 | 2025-03-04 | Uab Research Foundation | APOE mimetic peptides and higher potency to clear plasma cholesterol |
| EP3253785B1 (en) | 2015-02-06 | 2019-04-10 | Navigo Proteins Gmbh | Novel egfr binding proteins |
| WO2017009421A1 (en) | 2015-07-16 | 2017-01-19 | Scil Proteins Gmbh | Novel immunoglobulin-binding proteins and their use in affinity purification |
| US10584152B2 (en) | 2015-07-20 | 2020-03-10 | Navigo Proteins Gmbh | Binding proteins based on di-ubiquitin muteins and methods for generation |
| US11813336B2 (en) | 2016-05-04 | 2023-11-14 | Navigo Proteins Gmbh | Targeted compounds for the site-specific coupling of chemical moieties comprising a peptide linker |
| CN117736281A (zh) | 2016-08-11 | 2024-03-22 | 瑞普利金公司 | 用于亲和色谱的碱性稳定性fc结合蛋白 |
| TW201919686A (zh) | 2017-08-10 | 2019-06-01 | 法商塞勒尼斯醫療控股公司 | 脫輔基子(apomers) |
| EP3668600B1 (en) | 2017-08-10 | 2024-05-15 | Abionyx Pharma SA | Cargomers |
| US11414466B2 (en) | 2017-11-07 | 2022-08-16 | Navigo Proteins Gmbh | Fusion proteins with specificity for ED-B and long serum half-life for diagnosis or treatment of cancer |
| WO2020127224A1 (en) | 2018-12-18 | 2020-06-25 | Navigo Proteins Gmbh | Novel folr1 specific binding proteins for cancer diagnosis and treatment |
| JP2023522889A (ja) | 2020-04-16 | 2023-06-01 | アビオニクス ファーマ エスエー | 脂質結合タンパク質ベースの複合体を使用した、急性病態を治療するための方法 |
| JP2023543498A (ja) | 2020-10-01 | 2023-10-16 | アビオニクス ファーマ エスエー | 脂質結合タンパク質ベースの複合体を使用した、眼疾患を治療するための方法 |
| CN117479834A (zh) | 2021-04-15 | 2024-01-30 | 阿比奥尼克斯制药公司 | 基于脂质结合蛋白的复合物在器官保存溶液中的用途 |
| IL316110A (en) | 2022-04-06 | 2024-12-01 | Abionyx Pharma Sa | Methods for treating eye diseases using complexes based on fat-binding protein |
| WO2023194798A1 (en) | 2022-04-06 | 2023-10-12 | Abionyx Pharma Sa | Methods for treating leukocytosis, endothelial dysfunction and carditis using lipid binding protein-based complexes |
| CA3258787A1 (en) | 2022-06-10 | 2023-12-14 | Stanislas FAGUER | METHODS OF TREATMENT OF HYPERINFLAMMATORY DISEASES USING LIPID-BINDING PROTEIN COMPLEXES |
| EP4536269A2 (en) | 2022-06-10 | 2025-04-16 | Abionyx Pharma SA | Methods for treating acute conditions using lipid binding protein-based complexes |
| IL322074A (en) | 2023-01-13 | 2025-09-01 | Abionyx Pharma Sa | Treatment using a lipid-binding protein molecule |
| WO2025093929A1 (en) | 2023-10-31 | 2025-05-08 | Abionyx Pharma Sa | Lipid binding protein molecule therapy |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8625435D0 (en) * | 1986-10-23 | 1986-11-26 | Erba Farmitalia | Human apolipoprotein ai |
| IT1229996B (it) * | 1989-04-20 | 1991-09-20 | Cesare Sirtori | Espressione di apolipoproteina ai e apolipoproteina ai-milano in lievito e composizioni farmaceutiche che contengono dette apolipoproteine. |
| SE9103701D0 (sv) * | 1991-12-13 | 1991-12-13 | Kabi Pharmacia Ab | Apolipoprotein |
-
1991
- 1991-12-13 SE SE9103701A patent/SE9103701D0/xx unknown
-
1992
- 1992-11-20 ZA ZA928989A patent/ZA928989B/xx unknown
- 1992-12-03 IL IL10395692A patent/IL103956A/en not_active IP Right Cessation
- 1992-12-11 NZ NZ246223A patent/NZ246223A/en unknown
- 1992-12-11 AT AT93900484T patent/ATE242269T1/de not_active IP Right Cessation
- 1992-12-11 RU RU93054168A patent/RU2134696C1/ru not_active IP Right Cessation
- 1992-12-11 BR BR9205640A patent/BR9205640A/pt not_active Application Discontinuation
- 1992-12-11 CZ CZ19931589A patent/CZ289879B6/cs not_active IP Right Cessation
- 1992-12-11 WO PCT/SE1992/000858 patent/WO1993012143A1/en not_active Ceased
- 1992-12-11 PL PL92300262A patent/PL171907B1/pl not_active IP Right Cessation
- 1992-12-11 JP JP5510842A patent/JPH07502892A/ja active Pending
- 1992-12-11 DE DE69233092T patent/DE69233092T2/de not_active Expired - Lifetime
- 1992-12-11 EP EP93900484A patent/EP0571602B1/en not_active Expired - Lifetime
- 1992-12-11 HU HU9302344A patent/HU217203B/hu not_active IP Right Cessation
- 1992-12-11 RO RO93-01116A patent/RO115636B1/ro unknown
- 1992-12-11 PL PL92314894A patent/PL172544B1/pl not_active IP Right Cessation
- 1992-12-11 SK SK868-93A patent/SK86893A3/sk unknown
- 1992-12-11 US US08/104,063 patent/US5876968A/en not_active Expired - Lifetime
- 1992-12-11 PT PT93900484T patent/PT571602E/pt unknown
- 1992-12-11 MX MX9207224A patent/MX9207224A/es unknown
- 1992-12-11 SG SG1996001800A patent/SG47453A1/en unknown
- 1992-12-11 PL PL92314896A patent/PL172168B1/pl unknown
- 1992-12-11 DK DK93900484T patent/DK0571602T3/da active
- 1992-12-11 ES ES93900484T patent/ES2199939T3/es not_active Expired - Lifetime
- 1992-12-11 AU AU31755/93A patent/AU3175593A/en not_active Abandoned
- 1992-12-11 CA CA002103996A patent/CA2103996C/en not_active Expired - Fee Related
- 1992-12-11 NZ NZ280516A patent/NZ280516A/en unknown
-
1993
- 1993-08-11 BG BG98036A patent/BG61451B1/bg unknown
- 1993-08-12 NO NO19932866A patent/NO315076B1/no not_active IP Right Cessation
- 1993-08-12 FI FI933557A patent/FI115771B/fi not_active IP Right Cessation
-
1994
- 1994-11-16 EE EE9400375A patent/EE03058B1/xx unknown
-
1995
- 1995-06-30 HU HU95P/P00630P patent/HU211667A9/hu unknown
-
1996
- 1996-07-12 AU AU59473/96A patent/AU703283B2/en not_active Ceased
-
1999
- 1999-03-01 US US09/259,434 patent/US6617134B1/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO315076B1 (no) | Dimerpreparat av molekyl¶rvariant av apolipoprotein og fremgangsmåter for fremstilling og anvendelse derav, til fremstilling av et medikamentfor behandling av aterosklerose og kardiovaskul¶re sykdommer | |
| Morrow et al. | Functional characterization of apolipoprotein E isoforms overexpressed in Escherichia coli | |
| DK171278B1 (da) | DNA-Sekvens, vektor omfattende en sådan sekvens, værtsorganisme transformeret med en sådan vektor og fremgangmåde til fremstilling af et protein eller peptidprodukt ved hjælp deraf | |
| US7223726B2 (en) | Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same | |
| CA2428114A1 (en) | Apolipoprotein analogues | |
| JP2006223316A (ja) | 組換えフィブリン鎖、フィブリンおよびフィブリン−ホモログ | |
| JP4624495B2 (ja) | ヒト・インスリンの生成 | |
| JPS63119682A (ja) | 細胞増殖刺激剤 | |
| Sun et al. | Identification of lipid binding and lipoprotein lipase activation domains of human apoAV | |
| Lu et al. | Cloning, purification, and refolding of human paraoxonase-3 expressed in Escherichia coli and its characterization | |
| Ribó et al. | Purification of engineered human pancreatic ribonuclease | |
| Vilei et al. | Functional properties of recombinant calpain I and of mutants lacking domains III and IV of the catalytic subunit | |
| Sun et al. | Expression, purification and characterization of aprotinin and a human analogue of aprotinin | |
| US8968728B2 (en) | Chimeric fusion proteins | |
| Trachuk et al. | In vitro refolding of carboxypeptidase T precursor from Thermoactinomyces vulgaris obtained in Escherichia coli as cytoplasmic inclusion bodies | |
| JPH03259084A (ja) | トロンビン結合性物質の製造法 | |
| Rahman et al. | Expression of apolipoprotein (a) kringle IV type 9 in Escherichia coli: demonstration of a specific interaction between kringle IV type 9 and apolipoproteinB-100. | |
| JP3172968B2 (ja) | Il―16の多量体形態、それらを生産するための方法及びそれらの使用 | |
| Srivastava et al. | Characterization of a sodium deoxycholate-activatable proteinase activity associated with βA3/A1-crystallin of human lenses | |
| Nataraj et al. | Truncated Thioredoxin Peptides Serves as an Efficient Fusion Tag for Production of Proinsulin | |
| Lopez et al. | Purification and characterization of recombinant human apolipoprotein A‐II expressed in Escherichia coli | |
| JPH04234988A (ja) | ヒトプロラクチン−プロテインa融合蛋白発現遺伝子 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |