CA1203764A - Plasminogen activator derivatives - Google Patents
Plasminogen activator derivativesInfo
- Publication number
- CA1203764A CA1203764A CA000414556A CA414556A CA1203764A CA 1203764 A CA1203764 A CA 1203764A CA 000414556 A CA000414556 A CA 000414556A CA 414556 A CA414556 A CA 414556A CA 1203764 A CA1203764 A CA 1203764A
- Authority
- CA
- Canada
- Prior art keywords
- urokinase
- molecular weight
- glycol
- derivative
- triazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 102000001938 Plasminogen Activators Human genes 0.000 title claims abstract description 29
- 108010001014 Plasminogen Activators Proteins 0.000 title claims abstract description 29
- 229940127126 plasminogen activator Drugs 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 42
- 229920001515 polyalkylene glycol Polymers 0.000 claims abstract description 35
- 230000008569 process Effects 0.000 claims abstract description 19
- 239000007822 coupling agent Substances 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 230000002163 immunogen Effects 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 4
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 140
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 140
- 229960005356 urokinase Drugs 0.000 claims description 130
- -1 polyethylene Polymers 0.000 claims description 59
- 229920001223 polyethylene glycol Polymers 0.000 claims description 45
- 239000004698 Polyethylene Substances 0.000 claims description 44
- 229920000573 polyethylene Polymers 0.000 claims description 42
- 239000002202 Polyethylene glycol Substances 0.000 claims description 41
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 39
- 125000003827 glycol group Chemical group 0.000 claims description 28
- 239000004743 Polypropylene Substances 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
- 229920001451 polypropylene glycol Polymers 0.000 claims description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 14
- 229920001155 polypropylene Polymers 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 14
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 7
- 239000012190 activator Substances 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 230000001766 physiological effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 150000001346 alkyl aryl ethers Chemical class 0.000 claims 1
- 239000003527 fibrinolytic agent Substances 0.000 abstract description 4
- 229960000103 thrombolytic agent Drugs 0.000 abstract description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 60
- 230000000694 effects Effects 0.000 description 48
- 239000000243 solution Substances 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 30
- 238000001816 cooling Methods 0.000 description 25
- 239000008363 phosphate buffer Substances 0.000 description 21
- 239000000203 mixture Substances 0.000 description 17
- 238000000502 dialysis Methods 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 102000009123 Fibrin Human genes 0.000 description 13
- 108010073385 Fibrin Proteins 0.000 description 13
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 13
- 229950003499 fibrin Drugs 0.000 description 13
- 230000004048 modification Effects 0.000 description 13
- 238000012986 modification Methods 0.000 description 13
- 239000002504 physiological saline solution Substances 0.000 description 13
- 229920001281 polyalkylene Polymers 0.000 description 13
- 102000013566 Plasminogen Human genes 0.000 description 11
- 108010051456 Plasminogen Proteins 0.000 description 11
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 150000003918 triazines Chemical class 0.000 description 10
- 108010088842 Fibrinolysin Proteins 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 229940012957 plasmin Drugs 0.000 description 9
- 239000002806 plasmin inhibitor Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 108700023418 Amidases Proteins 0.000 description 8
- 229940122791 Plasmin inhibitor Drugs 0.000 description 8
- 102000005922 amidase Human genes 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000011369 resultant mixture Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000012891 Ringer solution Substances 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 235000019256 formaldehyde Nutrition 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007972 injectable composition Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 238000001226 reprecipitation Methods 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical compound C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 description 3
- OMRXVBREYFZQHU-UHFFFAOYSA-N 2,4-dichloro-1,3,5-triazine Chemical compound ClC1=NC=NC(Cl)=N1 OMRXVBREYFZQHU-UHFFFAOYSA-N 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 230000003480 fibrinolytic effect Effects 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- WFJRIDQGVSJLLH-UHFFFAOYSA-N methyl n-aminocarbamate Chemical compound COC(=O)NN WFJRIDQGVSJLLH-UHFFFAOYSA-N 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000010257 thawing Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 101710196208 Fibrinolytic enzyme Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- NCGJACBPALRHNG-UHFFFAOYSA-M sodium;2,4,6-trinitrobenzenesulfonate Chemical compound [Na+].[O-][N+](=O)C1=CC([N+]([O-])=O)=C(S([O-])(=O)=O)C([N+]([O-])=O)=C1 NCGJACBPALRHNG-UHFFFAOYSA-M 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- 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 1
- PPXUUPXQWDQNGO-UHFFFAOYSA-N 2-azidoacetic acid Chemical compound OC(=O)CN=[N+]=[N-] PPXUUPXQWDQNGO-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 1
- FKCZBCAVNSXTFW-UHFFFAOYSA-N 6-chloro-1h-1,3,5-triazin-2-one Chemical compound ClC1=NC=NC(=O)N1 FKCZBCAVNSXTFW-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 241000283986 Lepus Species 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 101001092200 Mus musculus RNA binding protein fox-1 homolog 3 Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193803 Therea Species 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003248 enzyme activator Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 201000005665 thrombophilia Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21073—Serine endopeptidases (3.4.21) u-Plasminogen activator (3.4.21.73), i.e. urokinase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6456—Plasminogen activators
- C12N9/6462—Plasminogen activators u-Plasminogen activator (3.4.21.73), i.e. urokinase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56-172908 | 1981-10-30 | ||
| JP56172908A JPS5896026A (ja) | 1981-10-30 | 1981-10-30 | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| CA000443230A CA1217718A (en) | 1981-10-30 | 1983-12-14 | Plasminogen activator derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1203764A true CA1203764A (en) | 1986-04-29 |
Family
ID=25670236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000414556A Expired CA1203764A (en) | 1981-10-30 | 1982-10-29 | Plasminogen activator derivatives |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4495285A (enExample) |
| JP (1) | JPS5896026A (enExample) |
| BR (1) | BR8206347A (enExample) |
| CA (1) | CA1203764A (enExample) |
| CH (1) | CH658669A5 (enExample) |
| DE (1) | DE3240174A1 (enExample) |
| FR (1) | FR2515684B1 (enExample) |
| GB (1) | GB2110219B (enExample) |
| SE (1) | SE457800B (enExample) |
Families Citing this family (199)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4609546A (en) * | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| JPS59196824A (ja) * | 1983-04-21 | 1984-11-08 | Kowa Co | 吸着防止剤 |
| JPS60176586A (ja) * | 1984-02-21 | 1985-09-10 | Sanwa Kagaku Kenkyusho:Kk | 新規な修飾ウロキナ−ゼ、その製法並びにこれを含有する血栓溶解剤 |
| GB8430252D0 (en) * | 1984-11-30 | 1985-01-09 | Beecham Group Plc | Compounds |
| US4732863A (en) * | 1984-12-31 | 1988-03-22 | University Of New Mexico | PEG-modified antibody with reduced affinity for cell surface Fc receptors |
| JPS61176532A (ja) * | 1985-01-30 | 1986-08-08 | Green Cross Corp:The | プラスミノ−ゲンアクチベ−タ−前駆体の安定化方法 |
| US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4844897A (en) * | 1985-09-13 | 1989-07-04 | Hiroshi Maeda | Anti-tumor protease preparations |
| JP2514950B2 (ja) * | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質，その製造法および中間体 |
| US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| DK468388A (da) * | 1987-08-21 | 1989-02-22 | Wellcome Found | Kompleks af polyethylenglycol og vaevplasminogen-aktivator, fremgangsmaade til dets fremstilling og farmaceutiske kompositioner indeholdende komplekset |
| US5306500A (en) * | 1988-11-21 | 1994-04-26 | Collagen Corporation | Method of augmenting tissue with collagen-polymer conjugates |
| US5162430A (en) * | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
| US5565519A (en) * | 1988-11-21 | 1996-10-15 | Collagen Corporation | Clear, chemically modified collagen-synthetic polymer conjugates for ophthalmic applications |
| US5510418A (en) * | 1988-11-21 | 1996-04-23 | Collagen Corporation | Glycosaminoglycan-synthetic polymer conjugates |
| US5166322A (en) * | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| US5998378A (en) * | 1989-08-16 | 1999-12-07 | Chiron Corporation | Compositions for the inhibition of TNF hormone formation and uses thereof |
| US5843693A (en) * | 1989-08-16 | 1998-12-01 | Chiron Corporation | Assay method for screening for inhibitors of proTNF conversion |
| US6586222B1 (en) | 1989-08-16 | 2003-07-01 | Chiron Corporation | Recombinant PR-3 and compositions thereof |
| IT1260468B (it) * | 1992-01-29 | 1996-04-09 | Metodo per mantenere l'attivita' di enzimi proteolitici modificati con polietilenglicole | |
| US20030171292A1 (en) * | 1992-06-01 | 2003-09-11 | Creasey Abla A. | Method for using lipoprotein associated coagulation inhibitor to treat sepsis |
| US6063764A (en) * | 1992-06-01 | 2000-05-16 | Washington University & Chiron Corp. | Method for using lipoprotein associated coagulation inhibitor to treat sepsis |
| JPH08502082A (ja) * | 1992-07-02 | 1996-03-05 | コラーゲン コーポレイション | 生体適合性ポリマー結合体 |
| AU687763B2 (en) * | 1992-10-20 | 1998-03-05 | Central Laboratory Of The Netherlands Red Cross Blood Transfusion Service | Interleukin-6 receptor antagonists |
| WO1995024501A1 (en) | 1994-03-07 | 1995-09-14 | Cetus Oncology Corporation | Compositions for the inhibition of tnf formation and uses thereof |
| US6458889B1 (en) | 1995-12-18 | 2002-10-01 | Cohesion Technologies, Inc. | Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use |
| US7883693B2 (en) * | 1995-12-18 | 2011-02-08 | Angiodevice International Gmbh | Compositions and systems for forming crosslinked biomaterials and methods of preparation of use |
| US6833408B2 (en) * | 1995-12-18 | 2004-12-21 | Cohesion Technologies, Inc. | Methods for tissue repair using adhesive materials |
| WO1997022371A1 (en) | 1995-12-18 | 1997-06-26 | Collagen Corporation | Crosslinked polymer compositions and methods for their use |
| DE69731836T2 (de) * | 1996-07-23 | 2005-12-01 | Pangenetics B.V. | Induzierung von t zell toleranz unter verwendung eines löslichen moleküls, dass gleichzeitig zwei kostimulierungswege blockieren kann |
| AU1727500A (en) * | 1998-11-17 | 2000-06-05 | Tanox, Inc. | Bispecific molecules cross-linking itim and itam for therapy |
| US7118743B2 (en) | 1998-11-17 | 2006-10-10 | Tanox, Inc. | Bispecific molecules cross-linking ITIM and ITAM for therapy |
| ATE449791T1 (de) | 2000-10-10 | 2009-12-15 | Genentech Inc | Inhibierung von c5 komplement-aktivierung für die behandlung und vorbeugung von xeno-transplantat oder akute vaskuläre abstossung |
| US20020182172A1 (en) * | 2000-11-30 | 2002-12-05 | Shearwater Corporation | Water-soluble polymer conjugates of triazine derivatives |
| US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
| EP1878441B1 (en) | 2001-08-17 | 2018-01-24 | Genentech, Inc. | Complement pathway inhibitors binding to C5 and C5a without preventing the formation of C5b |
| US7320789B2 (en) | 2001-09-26 | 2008-01-22 | Wyeth | Antibody inhibitors of GDF-8 and uses thereof |
| BR0213293A (pt) * | 2001-10-15 | 2004-12-21 | Chiron Corp | Uso de tfpi ou de um análogo de tfpi no tratamento de septicemia |
| PL374966A1 (en) | 2002-02-21 | 2005-11-14 | Wyeth | Follistatin domain containing proteins |
| AU2003303513A1 (en) * | 2002-12-30 | 2004-07-29 | Angiotech International Ag | Tissue reactive compounds and compositions and uses thereof |
| WO2004060346A2 (en) | 2002-12-30 | 2004-07-22 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| MXPA05009556A (es) * | 2003-03-14 | 2005-11-16 | Wyeth Corp | Anticuerpos contra receptor de il-21 humano y sus usos. |
| PL1682177T3 (pl) | 2003-11-04 | 2011-03-31 | Novartis Vaccines & Diagnostics Inc | Zastosowanie antagonistycznych przeciwciał anty-CD40 do leczenia przewlekłej białaczki limfocytowej |
| DK1680141T3 (da) | 2003-11-04 | 2010-11-01 | Novartis Vaccines & Diagnostic | Fremgangsmåder til terapi til faste tumorer der udtrykker CD40-celleoverfladeantigenet |
| US20070098718A1 (en) | 2003-11-04 | 2007-05-03 | Chiron | Methods of therapy for b cell-related cancers |
| PT1684805E (pt) | 2003-11-04 | 2010-10-26 | Novartis Vaccines & Diagnostic | Utilização de anticorpos monoclonais antagonistas anti-cd40 para o tratamento do mieloma múltiplo |
| AU2004287879C1 (en) | 2003-11-04 | 2011-05-26 | Novartis Vaccines And Diagnostics, Inc. | Antagonist anti-CD40 monoclonal antibodies and methods for their use |
| ES2689328T3 (es) | 2004-01-07 | 2018-11-13 | Novartis Vaccines And Diagnostics, Inc. | Anticuerpo monoclonal M-CSF-específico y usos del mismo |
| US20050169970A1 (en) * | 2004-02-02 | 2005-08-04 | Unilever Bestfoods, North America | Food composition with fibers |
| MXPA06010587A (es) * | 2004-03-17 | 2007-03-29 | Chiron Corp | Tratamiento de neumonia severa adquirida en comunidad por administracion del inhibidor de la via del factor tisular (tfpi). |
| NZ550964A (en) | 2004-04-28 | 2011-05-27 | Angiodevice Internat Gmbh | Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use |
| WO2006034128A2 (en) | 2004-09-17 | 2006-03-30 | Angiotech Biomaterials Corporation | Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use |
| DE602005022928D1 (de) | 2004-11-30 | 2010-09-23 | Abgenix Inc | Antikörper gegen gpnmb und ihre verwendungen |
| WO2006081171A1 (en) * | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
| EP2551282A3 (en) | 2005-03-23 | 2013-02-13 | Genmab A/S | Antibodies against CD38 for treatment of multiple myeloma |
| US20060269556A1 (en) * | 2005-04-18 | 2006-11-30 | Karl Nocka | Mast cell activation using siglec 6 antibodies |
| SG164379A1 (en) * | 2005-07-21 | 2010-09-29 | Genmab As | Potency assays for antibody drug substance binding to an fc receptor |
| US8652469B2 (en) * | 2005-07-28 | 2014-02-18 | Novartis Ag | M-CSF-specific monoclonal antibody and uses thereof |
| EP2277916A3 (en) * | 2005-07-28 | 2011-04-27 | Novartis AG | Use of antibody to M-CSF |
| EP1960431B1 (en) | 2005-12-15 | 2014-10-01 | Genmab A/S | Use of effector-function-deficient antibodies for treatment of auto-immune diseases |
| TWI417301B (zh) | 2006-02-21 | 2013-12-01 | Wyeth Corp | 對抗人類介白素-２２（ｉｌ-２２）之抗體及其用途 |
| TW200744634A (en) | 2006-02-21 | 2007-12-16 | Wyeth Corp | Methods of using antibodies against human IL-22 |
| JP2009529915A (ja) | 2006-03-20 | 2009-08-27 | ゾーマ テクノロジー リミテッド | ガストリン物質に対して特異的なヒト抗体および方法 |
| KR20090010194A (ko) | 2006-04-13 | 2009-01-29 | 노바티스 백신즈 앤드 다이아그노스틱스, 인크. | 암의 치료, 진단 또는 검출 방법 |
| TWI395754B (zh) | 2006-04-24 | 2013-05-11 | Amgen Inc | 人類化之ｃ-ｋｉｔ抗體 |
| DK2038306T3 (en) | 2006-06-30 | 2015-03-09 | Novo Nordisk As | ANTI-NKG2A ANTIBODIES AND APPLICATIONS THEREOF |
| RU2009107707A (ru) | 2006-08-04 | 2010-09-10 | Новартис АГ (CH) | СПЕЦИФИЧНОЕ К EphB3 АНТИТЕЛО И ЕГО ПРИМЕНЕНИЕ |
| CA2661023C (en) | 2006-08-18 | 2017-08-15 | Novartis Ag | Prlr-specific antibody and uses thereof |
| MX2009006034A (es) | 2006-12-07 | 2009-10-12 | Novartis Ag | Anticuerpos antagonistas contra ephb3. |
| WO2009077483A1 (en) | 2007-12-14 | 2009-06-25 | Novo Nordisk A/S | Antibodies against human nkg2d and uses thereof |
| GB0700133D0 (en) | 2007-01-04 | 2007-02-14 | Humabs Llc | Human cytomegalovirus neutralising antibodies and use thereof |
| PE20130588A1 (es) * | 2007-02-02 | 2013-05-21 | Amgen Inc | Hepcidina, antagonistas de la hepcidina y metodos de uso |
| WO2008112988A2 (en) | 2007-03-14 | 2008-09-18 | Novartis Ag | Apcdd1 inhibitors for treating, diagnosing or detecting cancer |
| WO2009085200A2 (en) | 2007-12-21 | 2009-07-09 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
| MX2010007935A (es) | 2008-01-24 | 2010-08-23 | Novo Nordisk As | Anticuerpo monoclonal humanizado anti-nkg2a humano. |
| EP2803675A3 (en) | 2008-01-25 | 2014-12-24 | Amgen, Inc | Ferroportin antibodies and methods of use |
| WO2009139822A1 (en) | 2008-05-01 | 2009-11-19 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
| AU2009246166B2 (en) | 2008-05-15 | 2014-09-18 | Tetherex Pharmaceuticals Corporation | Anti-PSGL-1 antibodies and methods of identification and use |
| AU2008359583B2 (en) | 2008-07-16 | 2012-04-05 | Institute For Research In Biomedicine | Human cytomegalovirus neutralising antibodies and use thereof |
| PE20141398A1 (es) | 2008-07-16 | 2014-10-18 | Inst Research In Biomedicine | Anticuerpos neutralizantes de citomegalovirus humano |
| CA2731686C (en) * | 2008-07-25 | 2020-04-07 | Institute For Research In Biomedicine | Neutralizing anti-influenza a virus antibodies and uses thereof |
| US8871207B2 (en) | 2008-07-25 | 2014-10-28 | Humabs, LLC | Neutralizing anti-influenza A virus antibodies and uses thereof |
| RU2011113405A (ru) * | 2008-09-08 | 2012-10-20 | Оттава Хоспитл Рисерч Инститьют (Ca) | Регенерация поджелудочной железы, индуцированная периостином |
| WO2010043977A2 (en) | 2008-10-13 | 2010-04-22 | Institute For Research In Biomedicine | Dengue virus neutralizing antibodies and uses thereof |
| UA109633C2 (uk) | 2008-12-09 | 2015-09-25 | Антитіло людини проти тканинного фактора | |
| JP2012521197A (ja) | 2009-03-20 | 2012-09-13 | アムジエン・インコーポレーテツド | 担体免疫グロブリンおよびその使用 |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| AU2010298036B2 (en) | 2009-09-25 | 2015-05-21 | Xoma Technology Ltd. | Screening methods |
| AU2010321832B2 (en) | 2009-11-20 | 2014-08-14 | Amgen Inc. | Anti-Orai1 antigen binding proteins and uses thereof |
| US20110212106A1 (en) | 2010-01-20 | 2011-09-01 | Institute For Research In Bioscience | Hiv-1 neutralizing antibodies and uses thereof |
| EP3904391B1 (en) | 2010-03-10 | 2024-07-10 | Genmab A/S | Monoclonal antibodies against c-met |
| NZ604007A (en) | 2010-05-27 | 2015-03-27 | Genmab As | Monoclonal antibodies against her2 epitope |
| IL299365A (en) | 2010-05-27 | 2023-02-01 | Genmab As | Monoclonal antibodies against 2HER |
| EP2580243B1 (en) | 2010-06-09 | 2019-10-16 | Genmab A/S | Antibodies against human cd38 |
| JP6055404B2 (ja) | 2010-06-15 | 2016-12-27 | ゲンマブ エー／エス | 組織因子に対するヒト抗体薬物結合体 |
| CA2885176C (en) | 2010-09-22 | 2018-10-23 | Amgen Inc. | Carrier immunoglobulins and uses thereof |
| AR083847A1 (es) | 2010-11-15 | 2013-03-27 | Novartis Ag | Variantes de fc (fragmento constante) silenciosas de los anticuerpos anti-cd40 |
| JP6069212B2 (ja) | 2010-12-02 | 2017-02-01 | ビオノール イミュノ エーエスＢｉｏｎｏｒ Ｉｍｍｕｎｏ Ａｓ | ペプチド骨格設計 |
| EP3222635A1 (en) | 2010-12-21 | 2017-09-27 | Selexys Pharmaceuticals Corporation | Anti-p-selectin antibodies and methods of their use and identification |
| JP6294076B2 (ja) | 2011-01-06 | 2018-03-14 | ビオノール イミュノ エーエスＢｉｏｎｏｒ Ｉｍｍｕｎｏ Ａｓ | 多量体ペプチド |
| WO2012136552A1 (en) | 2011-04-08 | 2012-10-11 | H. Lundbeck A/S | ANTIBODIES SPECIFIC TO PYROGLUTAMATED Αβ |
| EP2699260B1 (en) | 2011-04-20 | 2024-11-20 | Genmab A/S | Bispecifc antibodies against her2 |
| CA2832387A1 (en) | 2011-04-20 | 2012-10-26 | Genmab A/S | Bispecifc antibodies against her2 |
| EP2714735B1 (en) | 2011-06-03 | 2021-07-21 | XOMA Technology Ltd. | Antibodies specific for tgf-beta |
| UA117901C2 (uk) | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
| HUE044089T2 (hu) | 2011-07-18 | 2019-09-30 | Inst Res Biomedicine | Neutralizáló anti-influenza A antitestek és alkalmazásaik |
| KR102149069B1 (ko) | 2012-03-20 | 2020-08-28 | 후맙스 바이오메드 에스에이 | Rsv, mpv 및 pvm를 중화하는 항체 및 이의 용도 |
| WO2013182661A1 (en) | 2012-06-06 | 2013-12-12 | Bionor Immuno As | Peptides derived from viral proteins for use as immunogens and dosage reactants |
| WO2014006217A1 (en) | 2012-07-06 | 2014-01-09 | Genmab B.V. | Dimeric protein with triple mutations |
| EP3632462A1 (en) | 2012-07-06 | 2020-04-08 | Genmab B.V. | Dimeric protein with triple mutations |
| UA105278C2 (ru) | 2012-09-06 | 2014-04-25 | Інститут Біології Клітини Нан України | Способ получения каталитически активных антител (абзимов) с сиалидазной активностью |
| MX387324B (es) | 2013-01-10 | 2025-03-18 | Genmab Bv | Variantes de regiones fc de igg1 de humano y usos de las mismas. |
| TWI682941B (zh) | 2013-02-01 | 2020-01-21 | 美商再生元醫藥公司 | 含嵌合恆定區之抗體 |
| EA201591700A1 (ru) | 2013-03-14 | 2015-12-30 | Ридженерон Фармасьютикалз, Инк. | Гибридные белки апелина и их применение |
| CA2904357C (en) | 2013-03-15 | 2020-09-22 | Intrinsic Lifesciences Llc | Anti-hepcidin antibodies and uses thereof |
| SG11201602522VA (en) | 2013-10-02 | 2016-04-28 | Medimmune Llc | Neutralizing anti-influenza a antibodies and uses thereof |
| WO2015109264A1 (en) | 2014-01-17 | 2015-07-23 | Cedars-Sinai Medical Center | Receptor targeting constructs and uses thereof |
| EP3166688B1 (en) | 2014-07-08 | 2024-08-21 | New York University | Tau imaging ligands and their uses in the diagnosis and treatment of tauopathy |
| DK3169706T3 (da) | 2014-07-11 | 2020-03-09 | Genmab As | Antistoffer, der binder axl |
| WO2016011035A2 (en) | 2014-07-15 | 2016-01-21 | Medlmmune, Llc | Neutralizing anti-influenza b antibodies and uses thereof |
| WO2016013751A1 (ko) | 2014-07-22 | 2016-01-28 | 주식회사 레모넥스 | 생리활성 물질 또는 단백질 전달용 조성물 및 이의 용도 |
| SG10202102467RA (en) | 2014-07-24 | 2021-04-29 | Genentech Inc | Methods of conjugating an agent to a thiol moiety in a protein that contains at least one trisulfide bond |
| CA2961917A1 (en) | 2014-09-22 | 2016-03-31 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
| US20170296650A1 (en) | 2014-10-08 | 2017-10-19 | Novartis Ag | Combination of human cytomegalovirus neutralizing antibodies |
| DK3209778T3 (da) | 2014-10-24 | 2019-05-27 | Astrazeneca | Kombination |
| CN107106669A (zh) | 2014-11-04 | 2017-08-29 | 南加利福尼亚大学 | 用于治疗过度表达HIF‑1α的癌症的组合物和方法 |
| WO2016075546A2 (en) | 2014-11-14 | 2016-05-19 | Antonio Lanzavecchia | Antibodies that neutralize ebola virus and uses thereof |
| EP3831404B1 (en) | 2014-11-18 | 2026-01-28 | Humabs Biomed S.A. | Antibodies that potently neutralize rabies virus and other lyssaviruses and uses thereof |
| CA2971734C (en) | 2014-12-22 | 2025-11-18 | Pd-1 Acquisition Group, Llc | Anti-pd-1 antibodies |
| DK3277725T3 (da) | 2015-03-30 | 2021-01-11 | Regeneron Pharma | Konstante tungkædeområder med reduceret binding til FC-gammareceptorer |
| US10441644B2 (en) | 2015-05-05 | 2019-10-15 | The Regents Of The University Of California | H3.3 CTL peptides and uses thereof |
| EP3800199B1 (en) | 2015-05-05 | 2024-08-21 | The Regents of The University of California | H3.3 ctl peptides and uses thereof |
| US20160347848A1 (en) | 2015-05-28 | 2016-12-01 | Medimmune Limited | Therapeutic combinations and methods for treating neoplasia |
| MX389708B (es) | 2015-06-01 | 2025-03-20 | Medimmune Llc | Neutralizacion de moleculas de union anti-influenza y usos de las mismas. |
| WO2016207402A1 (en) | 2015-06-26 | 2016-12-29 | Institute For Research In Biomedicine | Proteins comprising a mutated lair-1 fragment and uses thereof |
| CA2991805A1 (en) | 2015-07-10 | 2017-01-19 | Genmab A/S | Axl-specific antibody-drug conjugates for cancer treatment |
| GB201512215D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
| JO3711B1 (ar) | 2015-07-13 | 2021-01-31 | H Lundbeck As | أجسام مضادة محددة لبروتين تاو وطرق استعمالها |
| GB201512203D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
| PT3334761T (pt) | 2015-08-13 | 2023-08-17 | Univ New York | Moléculas baseadas em anticorpo seletivo para o epítopo {p}ser404 da tau e os seus usos no diagnóstico e tratamento de tauopatias |
| US10988528B2 (en) | 2015-08-13 | 2021-04-27 | New York University | Antibody-based molecules specific for the truncated ASP421 epitope of Tau and their uses in the diagnosis and treatment of tauopathy |
| WO2017059878A1 (en) | 2015-10-07 | 2017-04-13 | Humabs Biomed Sa | Antibodies that potently neutralize hepatitis b virus and uses thereof |
| WO2017062966A1 (en) | 2015-10-09 | 2017-04-13 | Florida State University Research Foundation, Inc. | Antibodies specific for 4,6-diamino-5-(formyulamino) pyrimidine and uses thereof |
| UY36990A (es) | 2015-11-21 | 2017-11-30 | Fundació Privada Inst De Recerca De La Sida-Caixa (Irsicaixa) | Derivados de anticuerpos contra el vih con actividad dual antiviral e inmunomodulatoria |
| JP2019502715A (ja) | 2016-01-13 | 2019-01-31 | メディミューン，エルエルシー | Ａ型インフルエンザを治療する方法 |
| JP7029415B2 (ja) | 2016-07-12 | 2022-03-03 | ハー・ルンドベック・アクチエゼルスカベット | 過リン酸化タウに特異的な抗体およびその使用方法 |
| WO2018010789A1 (en) | 2016-07-13 | 2018-01-18 | Humabs Biomed Sa | Novel antibodies specifically binding to zika virus epitopes and uses thereof |
| EP3523330A1 (en) | 2016-10-04 | 2019-08-14 | Fairbanks Pharmaceuticals, Inc. | Anti-fstl3 antibodies and uses thereof |
| EP3535291A1 (en) | 2016-11-01 | 2019-09-11 | Genmab B.V. | Polypeptide variants and uses thereof |
| RU2019114679A (ru) | 2016-11-15 | 2020-12-17 | Х. Лундбекк А/С | Средства, пути применения и способы лечения синуклеопатии |
| EP3329905A1 (en) | 2016-12-05 | 2018-06-06 | Nuritas Limited | Topical cosmetic compositions comprising an oligopeptide against anti-aging of the skin |
| EP3329930A1 (en) | 2016-12-05 | 2018-06-06 | Nuritas Limited | Pharmaceuctical compositions |
| ES3057136T3 (en) | 2016-12-05 | 2026-02-26 | Nuritas Ltd | Compositions comprising peptide wkdeagkplvk |
| EP3555127B1 (en) | 2016-12-16 | 2024-12-18 | H. Lundbeck A/S | Agents, uses and methods |
| US10364286B2 (en) | 2016-12-22 | 2019-07-30 | H. Lundbeck A/S | Monoclonal anti-alpha-synuclein antibodies for preventing tau aggregation |
| US10995137B2 (en) | 2017-01-04 | 2021-05-04 | H. Lundbeck A/S | Antibodies specific for hyperphosphorlated tau for the treatment of ocular diseases |
| WO2018143787A1 (ko) | 2017-02-06 | 2018-08-09 | 주식회사 레모넥스 | 생리활성물질 전달체 |
| JP6883354B2 (ja) | 2017-02-06 | 2021-06-09 | レモネックス インコーポレイテッドＬｅｍｏｎｅｘ Ｉｎｃ． | 生理活性物質送達体 |
| EP3612562A2 (en) | 2017-04-19 | 2020-02-26 | Institute for Research in Biomedicine | Plasmodium sporozoite npdp peptides as vaccine and target novel malaria vaccines and antibodies binding to |
| US20200157192A1 (en) | 2017-05-10 | 2020-05-21 | Albajuna Therapeutics, S.L. | Fc-fusion protein derivatives with high dual hiv antiviral and immunomodulatory activity |
| US10894833B2 (en) | 2017-07-20 | 2021-01-19 | H. Lundbeck A/S | Agents, uses and methods for treatment |
| CN111201030B (zh) | 2017-07-25 | 2024-11-01 | 真和制药有限公司 | 通过阻断tim-3和其配体的相互作用治疗癌症 |
| WO2019042555A1 (en) | 2017-08-31 | 2019-03-07 | Humabs Biomed Sa | MULTISPECIFIC ANTIBODIES SPECIFICALLY BINDING TO ZIKA VIRUS EPITOPES AND USES THEREOF |
| KR102152348B1 (ko) | 2017-09-05 | 2020-09-08 | 주식회사 레모넥스 | 세포 운명 조절용 조성물 |
| US12649798B2 (en) | 2018-01-24 | 2026-06-09 | Genmab B.V. | Polypeptide variants and uses thereof |
| EP3752195A4 (en) | 2018-02-14 | 2021-11-17 | Viela Bio, Inc. | FELINE MCDONOUGH'S SARCOMA (FMS) -LIKE TYROSINKINASE-3 RECEPTOR LIGANDS (FLT3L) ANTIBODIES AND USES THEREOF IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES |
| JP7431750B2 (ja) | 2018-04-30 | 2024-02-15 | 武田薬品工業株式会社 | カンナビノイド受容体１型（ｃｂ１）結合性タンパク質及びその使用 |
| EP3820498A1 (en) | 2018-06-14 | 2021-05-19 | University College Cork-National University of Ireland Cork | Peptide for disease treatment |
| WO2020021061A1 (en) | 2018-07-26 | 2020-01-30 | Pieris Pharmaceuticals Gmbh | Humanized anti-pd-1 antibodies and uses thereof |
| SI3898668T1 (sl) | 2018-12-19 | 2024-02-29 | Humabs Biomed Sa | Protitelesa, ki nevtralizirajo virus hepatitisa B in njihove uporabe |
| KR20210124308A (ko) | 2019-01-30 | 2021-10-14 | 트루바인딩 아이엔씨. | 항-gal3 항체 및 이의 용도 |
| WO2020176771A1 (en) | 2019-02-27 | 2020-09-03 | Ionis Pharmaceuticals, Inc. | Modulators of malat1 expression |
| CA3131705A1 (en) | 2019-03-27 | 2020-10-01 | Umc Utrecht Holding B.V. | Engineered iga antibodies and methods of use |
| MX2021012171A (es) | 2019-04-09 | 2021-12-10 | Abcuro Inc | Anticuerpos reductores del miembro 1 de la subfamilia g de receptores similares a la lectina de linfocitos citoliticos (klrg1). |
| JP2022545265A (ja) | 2019-08-20 | 2022-10-26 | ニューリタス リミテッド | 筋萎縮を治療するためのペプチド |
| EP3783012A1 (en) | 2019-08-20 | 2021-02-24 | Nuritas Limited | An antimicrobial peptide |
| US20220380441A1 (en) | 2019-08-29 | 2022-12-01 | Vir Biotechnology, Inc. | Antibody compositions and methods for treating hepatitis b virus infection |
| MX2022004872A (es) | 2019-10-22 | 2022-05-13 | Nuritas Ltd | Tratamiento de enfermedad de higado graso no alcoholico. |
| EP3862014A1 (en) | 2020-02-07 | 2021-08-11 | Nuritas Limited | Treatment of panx1 associated diseases |
| US20230109142A1 (en) | 2020-02-14 | 2023-04-06 | Immunor As | Corona virus vaccine |
| MX2022014786A (es) | 2020-05-26 | 2023-01-16 | Truebinding Inc | Metodos para tratar enfermedades inflamatorias mediante el bloqueo de galectina-3. |
| BR112022026316A2 (pt) | 2020-06-24 | 2023-03-07 | Vir Biotechnology Inc | Anticorpos neutralizantes do vírus da hepatite b engenheirados e usos dos mesmos |
| US20250277031A1 (en) | 2021-01-08 | 2025-09-04 | Beijing Hanmi Pharmaceutical Co., Ltd. | Antibody specifically binding to cd47 and antigen-binding fragment thereof |
| US20240301068A1 (en) | 2021-01-08 | 2024-09-12 | Beijing Hanmi Pharmaceutical Co., Ltd. | Antibody specifically binding with pd-l1 and antigen-binding fragment of antibody |
| KR20230129484A (ko) | 2021-01-08 | 2023-09-08 | 베이징 한미 파마슈티컬 컴퍼니 리미티드 | 4-1bb와 특이적으로 결합하는 항체 및 그 항원 결합단편 |
| JP2024504167A (ja) | 2021-01-26 | 2024-01-30 | ヴィア・バイオテクノロジー・インコーポレイテッド | Ｂ型肝炎ウイルス感染を処置するための抗体組成物および方法 |
| CA3212311A1 (en) | 2021-03-26 | 2022-09-29 | Abcuro, Inc. | Anti-klrg1 antibodies |
| WO2022204529A1 (en) | 2021-03-26 | 2022-09-29 | Abcuro, Inc. | Anti-klrg1 antibodies |
| WO2022212836A1 (en) | 2021-04-01 | 2022-10-06 | Pyxis Oncology, Inc. | Gpnmb antibodies and methods of use |
| CN117642176A (zh) | 2021-04-14 | 2024-03-01 | 爱尔兰国立科克大学 | Psg1用于治疗骨关节炎 |
| WO2022219008A1 (en) | 2021-04-14 | 2022-10-20 | University College Cork - National University Of Ireland, Cork | Treatment of cerebrovascular events and neurological disorders |
| AU2022320627A1 (en) | 2021-07-26 | 2024-02-08 | Abcuro, Inc. | Killer cell lectin-like receptor subfamily g member 1 (klrg1) depleting antibodies |
| WO2023105281A1 (en) | 2021-12-11 | 2023-06-15 | Fundaciò Privada Institut De Recerca De La Sida-Caixa | Soluble tigit recombinant proteins |
| CN117586388A (zh) | 2022-08-09 | 2024-02-23 | 深圳智源生物医药有限公司 | 改进的β淀粉样蛋白寡聚体特异性结合抗体 |
| CN117589996A (zh) | 2022-08-09 | 2024-02-23 | 深圳智源生物医药有限公司 | 强毒性淀粉样蛋白寡聚体的诊断用途 |
| JP2025534040A (ja) | 2022-10-14 | 2025-10-09 | ユニバーシティ・カレッジ・コークーナショナル・ユニバーシティ・オブ・アイルランド，コーク | 腱傷害の治療における使用のための胎盤発現タンパク質 |
| WO2025147544A1 (en) | 2024-01-02 | 2025-07-10 | Abcuro, Inc. | Methods of treating inclusion body myositis (ibm) |
| WO2026072990A1 (en) | 2024-09-27 | 2026-04-02 | Abcuro, Inc. | Methods of treating t-cell large granular lymphocytic leukemia |
| WO2026112457A2 (en) | 2024-11-21 | 2026-05-28 | Regeneron Pharmaceuticals, Inc. | Heterodimeric antigen-binding molecules that bind to viral particles and uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2222080A1 (en) * | 1973-03-22 | 1974-10-18 | Viejo Jacques | Stabilisation of pepsin - by salt formation with a carboxy polymethylene |
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS5623587A (en) * | 1979-08-03 | 1981-03-05 | Mitsuwa Seiki Co Ltd | Vane type compressor |
| SU1022988A1 (ru) * | 1979-09-28 | 1983-06-15 | Всесоюзный кардиологический научный центр АМН СССР | Стабилизированна урокиназа,обладающа тромболитической активностью,и способ ее получени |
-
1981
- 1981-10-30 JP JP56172908A patent/JPS5896026A/ja active Granted
-
1982
- 1982-10-27 BR BR8206347A patent/BR8206347A/pt unknown
- 1982-10-27 US US06/437,009 patent/US4495285A/en not_active Expired - Fee Related
- 1982-10-28 CH CH6304/82A patent/CH658669A5/fr not_active IP Right Cessation
- 1982-10-29 GB GB08230987A patent/GB2110219B/en not_active Expired
- 1982-10-29 SE SE8206173A patent/SE457800B/sv not_active IP Right Cessation
- 1982-10-29 DE DE19823240174 patent/DE3240174A1/de active Granted
- 1982-10-29 CA CA000414556A patent/CA1203764A/en not_active Expired
- 1982-10-29 FR FR8218223A patent/FR2515684B1/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| SE8206173L (sv) | 1983-05-01 |
| DE3240174A1 (de) | 1983-05-19 |
| SE8206173D0 (sv) | 1982-10-29 |
| DE3240174C2 (enExample) | 1990-08-23 |
| US4495285A (en) | 1985-01-22 |
| JPS5896026A (ja) | 1983-06-07 |
| BR8206347A (pt) | 1983-09-27 |
| JPH0525470B2 (enExample) | 1993-04-13 |
| GB2110219B (en) | 1985-01-09 |
| CH658669A5 (fr) | 1986-11-28 |
| FR2515684A1 (fr) | 1983-05-06 |
| SE457800B (sv) | 1989-01-30 |
| US4495285B1 (enExample) | 1986-09-23 |
| GB2110219A (en) | 1983-06-15 |
| FR2515684B1 (fr) | 1986-04-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4495285A (en) | Plasminogen activator derivatives | |
| CA1217718A (en) | Plasminogen activator derivatives | |
| EP0200467B1 (en) | Superoxide dismutase combined with a poly(alkylene oxide) | |
| US6113896A (en) | Pharmaceutical compositions containing ecotin and homologs thereof | |
| JPH0696541B2 (ja) | アルファ―１―プロティナーゼ阻害剤と水溶性ポリマーとの共有結合した複合体の製造方法 | |
| PT950096E (pt) | Fragmentos de urocinase anti-invasivos e anti-angiogénicos e a sua utilização | |
| JPH09509838A (ja) | クニッツドメイン拮抗剤蛋白質 | |
| Santanché et al. | The unusual stability of saporin, a candidate for the synthesis of immunotoxins | |
| CA1271718A (en) | Fibrinolytic enzyme derivatives | |
| JPS60252422A (ja) | ハイブリツド蛋白質、その製法及びそれを含む医薬組成物 | |
| Smith et al. | Acyl-enzymes as thrombolytic agents in a rabbit model of venous thrombosis | |
| JPH07509229A (ja) | ウシ膵トリプシン阻害因子から誘導される因子Ｘａの阻害因子 | |
| WO1992019279A1 (en) | Phospholipid-targeted thrombolytic agents | |
| CA2067224C (en) | Hirudin/polyalkylene glycol conjugates | |
| US4082612A (en) | Plasminogen activator complex | |
| US4996050A (en) | Fibrinolytic activity enhancer | |
| US6875755B2 (en) | Antithrombotic compound | |
| WO1990003390A1 (en) | Peptidyl inhibitors of the initiation of coagulation | |
| WO1999065934A1 (en) | Antithrombotic compounds | |
| US4507283A (en) | Pharmacologically active compounds | |
| WO1985000521A1 (en) | Enzyme derivatives | |
| CA1182061A (en) | Superoxide dismutase, its production and use | |
| CA1283047C (en) | Stabilized plasminogen activator precursor and method of producing the same | |
| WO1992018139A1 (en) | Chimeric molecule with plasminogen activator activity and affinity for atherosclerotic plaques | |
| US20020031518A1 (en) | Plasminogen fragment having activity to inhibit tumor metastasis and growth and process for preparing same technical field |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |