LT3174B - Polyethylene glycol -interferon conjugates - Google Patents
Polyethylene glycol -interferon conjugates Download PDFInfo
- Publication number
- LT3174B LT3174B LTIP888A LTIP888A LT3174B LT 3174 B LT3174 B LT 3174B LT IP888 A LTIP888 A LT IP888A LT IP888 A LTIP888 A LT IP888A LT 3174 B LT3174 B LT 3174B
- Authority
- LT
- Lithuania
- Prior art keywords
- interferon
- conjugate
- cho
- peg
- compound
- Prior art date
Links
- 229940079322 interferon Drugs 0.000 title claims abstract description 97
- 229920001223 polyethylene glycol Polymers 0.000 title abstract description 48
- 239000002202 Polyethylene glycol Substances 0.000 title abstract description 45
- 102000014150 Interferons Human genes 0.000 claims abstract description 92
- 108010050904 Interferons Proteins 0.000 claims abstract description 92
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000003277 amino group Chemical group 0.000 claims description 24
- 229920000642 polymer Polymers 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 208000031295 Animal disease Diseases 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 150000002334 glycols Chemical class 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 2
- 235000018102 proteins Nutrition 0.000 description 48
- 102000004169 proteins and genes Human genes 0.000 description 48
- 108090000623 proteins and genes Proteins 0.000 description 48
- 239000003153 chemical reaction reagent Substances 0.000 description 39
- -1 poly (oxy-1,2-ethanediyl Chemical group 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 238000009833 condensation Methods 0.000 description 11
- 230000005494 condensation Effects 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical group CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 5
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 5
- 235000011130 ammonium sulphate Nutrition 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- GCSAXWHQFYOIFE-UHFFFAOYSA-N dipyridin-2-yl carbonate Chemical compound C=1C=CC=NC=1OC(=O)OC1=CC=CC=N1 GCSAXWHQFYOIFE-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- PVVTWNMXEHROIA-UHFFFAOYSA-N 2-(3-hydroxypropyl)-1h-quinazolin-4-one Chemical compound C1=CC=C2NC(CCCO)=NC(=O)C2=C1 PVVTWNMXEHROIA-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 229940047124 interferons Drugs 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010068370 Glutens Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 239000012506 Sephacryl® Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 235000021312 gluten Nutrition 0.000 description 2
- 125000003827 glycol group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000002594 sorbent Substances 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- AMLFJZRZIOZGPW-NSCUHMNNSA-N (e)-prop-1-en-1-amine Chemical compound C\C=C\N AMLFJZRZIOZGPW-NSCUHMNNSA-N 0.000 description 1
- HRGUSFBJBOKSML-UHFFFAOYSA-N 3',5'-di-O-methyltricetin Chemical compound COC1=C(O)C(OC)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 HRGUSFBJBOKSML-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- IDDMFNIRSJVBHE-UHFFFAOYSA-N Piscigenin Natural products COC1=C(O)C(OC)=CC(C=2C(C3=C(O)C=C(O)C=C3OC=2)=O)=C1 IDDMFNIRSJVBHE-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- AFFYTLSODCIHIH-UHFFFAOYSA-N bis(3-methylpyridin-2-yl) carbonate Chemical compound CC1=CC=CN=C1OC(=O)OC1=NC=CC=C1C AFFYTLSODCIHIH-UHFFFAOYSA-N 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940125890 compound Ia Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- VNKYTQGIUYNRMY-UHFFFAOYSA-N methoxypropane Chemical compound CCCOC VNKYTQGIUYNRMY-UHFFFAOYSA-N 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical class ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- BMCJATLPEJCACU-UHFFFAOYSA-N tricin Natural products COc1cc(OC)c(O)c(c1)C2=CC(=O)c3c(O)cc(O)cc3O2 BMCJATLPEJCACU-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/96—Esters of carbonic or haloformic acids
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/56—IFN-alpha
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/935,770 US5382657A (en) | 1992-08-26 | 1992-08-26 | Peg-interferon conjugates |
Publications (2)
Publication Number | Publication Date |
---|---|
LTIP888A LTIP888A (lt) | 1994-08-25 |
LT3174B true LT3174B (en) | 1995-02-27 |
Family
ID=25467637
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LTIP888A LT3174B (en) | 1992-08-26 | 1993-08-25 | Polyethylene glycol -interferon conjugates |
Country Status (37)
Country | Link |
---|---|
US (1) | US5382657A (no) |
EP (1) | EP0593868B1 (no) |
JP (1) | JP2859105B2 (no) |
KR (1) | KR100295520B1 (no) |
CN (3) | CN1183112C (no) |
AT (1) | ATE165102T1 (no) |
AU (1) | AU668742B2 (no) |
BG (1) | BG98067A (no) |
BR (1) | BR9303469A (no) |
CA (1) | CA2103829C (no) |
CZ (1) | CZ169393A3 (no) |
DE (1) | DE69317979T2 (no) |
DK (1) | DK0593868T3 (no) |
EE (1) | EE9400151A (no) |
ES (1) | ES2116376T3 (no) |
FI (1) | FI109765B (no) |
HR (1) | HRP931094A2 (no) |
HU (1) | HUT67013A (no) |
IL (1) | IL106750A0 (no) |
IS (1) | IS4067A (no) |
LT (1) | LT3174B (no) |
LV (1) | LV10907B (no) |
MW (1) | MW7693A1 (no) |
MX (1) | MX9305146A (no) |
MY (1) | MY131445A (no) |
NO (1) | NO933028D0 (no) |
NZ (2) | NZ264872A (no) |
OA (1) | OA09850A (no) |
PH (1) | PH30460A (no) |
PL (1) | PL300194A1 (no) |
RO (1) | RO112730B1 (no) |
SI (1) | SI9300423A (no) |
SK (1) | SK89893A3 (no) |
UY (1) | UY23635A1 (no) |
YU (1) | YU56693A (no) |
ZA (1) | ZA936098B (no) |
ZW (1) | ZW11193A1 (no) |
Families Citing this family (288)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2989002B2 (ja) * | 1988-12-22 | 1999-12-13 | キリン―アムジエン・インコーポレーテツド | 化学修飾顆粒球コロニー刺激因子 |
US7264944B1 (en) | 1989-04-21 | 2007-09-04 | Amgen Inc. | TNF receptors, TNF binding proteins and DNAs coding for them |
ES2238070T3 (es) * | 1989-04-21 | 2005-08-16 | Amgen Inc. | Receptor del tnf, proteina ligante del tnf y adn codante para estos. |
US6143866A (en) * | 1989-07-18 | 2000-11-07 | Amgen, Inc. | Tumor necrosis factor (TNF) inhibitor and method for obtaining the same |
IL95031A (en) | 1989-07-18 | 2007-03-08 | Amgen Inc | A method of producing a recombinant human necrotic factor absorber |
US6552170B1 (en) * | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US5880131A (en) * | 1993-10-20 | 1999-03-09 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
US5919455A (en) * | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
EP0730470B1 (en) * | 1993-11-10 | 2002-03-27 | Enzon, Inc. | Improved interferon polymer conjugates |
DK1090645T3 (da) * | 1994-02-08 | 2006-03-27 | Amgen Inc | Oral tilförsel af kemisk modificerede proteiner |
US5730990A (en) * | 1994-06-24 | 1998-03-24 | Enzon, Inc. | Non-antigenic amine derived polymers and polymer conjugates |
US20030053982A1 (en) * | 1994-09-26 | 2003-03-20 | Kinstler Olaf B. | N-terminally chemically modified protein compositions and methods |
DE4435087A1 (de) * | 1994-09-30 | 1996-04-04 | Deutsches Krebsforsch | Konjugat zur Behandlung von Infektions-, Autoimmun- und Hauterkrankungen |
US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
US5738846A (en) * | 1994-11-10 | 1998-04-14 | Enzon, Inc. | Interferon polymer conjugates and process for preparing the same |
TW426523B (en) * | 1995-04-06 | 2001-03-21 | Hoffmann La Roche | Interferon solution |
DE19514087A1 (de) * | 1995-04-13 | 1996-10-17 | Deutsches Krebsforsch | Konjugat aus einem Wirkstoff, einem Polyether und ggfs. einem nicht als körperfremd angesehenen, nativen Protein |
DK0858343T3 (da) | 1995-11-02 | 2004-05-10 | Schering Corp | Kontinuerlig lavdosis cytokininfusionsterapi |
US5908621A (en) * | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
TW517067B (en) * | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
TW555765B (en) * | 1996-07-09 | 2003-10-01 | Amgen Inc | Low molecular weight soluble tumor necrosis factor type-I and type-II proteins |
US7495087B2 (en) | 1997-07-14 | 2009-02-24 | Bolder Biotechnology, Inc. | Cysteine muteins in the C-D loop of human interleukin-11 |
WO1999003887A1 (en) * | 1997-07-14 | 1999-01-28 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
US6753165B1 (en) * | 1999-01-14 | 2004-06-22 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
US20080076706A1 (en) | 1997-07-14 | 2008-03-27 | Bolder Biotechnology, Inc. | Derivatives of Growth Hormone and Related Proteins, and Methods of Use Thereof |
US7270809B2 (en) * | 1997-07-14 | 2007-09-18 | Bolder Biotechnology, Inc. | Cysteine variants of alpha interferon-2 |
KR100364938B1 (ko) * | 1997-09-18 | 2002-12-18 | 에프. 호프만-라 로슈 아게 | 만성 씨형 간염의 치료를 위한 인테페론-알파와 아만타딘을 함유한 약제 |
EP1037649B1 (en) | 1997-12-17 | 2009-09-30 | Enzon, Inc. | Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents |
US6180095B1 (en) * | 1997-12-17 | 2001-01-30 | Enzon, Inc. | Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents |
US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
US5981709A (en) * | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
FR2774687B1 (fr) * | 1998-02-06 | 2002-03-22 | Inst Nat Sante Rech Med | Lipopeptides contenant un fragment de l'interferon gamma, et leur utilisation dans des compositions pharmaceutiques |
US6180096B1 (en) | 1998-03-26 | 2001-01-30 | Schering Corporation | Formulations for protection of peg-interferon alpha conjugates |
IL138221A0 (en) * | 1998-03-26 | 2001-10-31 | Schering Corp | Formulations for protection of peg-interferon alpha conjugates |
SK286654B6 (sk) | 1998-04-28 | 2009-03-05 | Laboratoires Serono Sa | Spôsob postupného pripájania polyetylénglykolových častí a použitie PEG-polypeptidových konjugátov vyrobených týmto spôsobom |
EP1213029A1 (en) | 1998-05-15 | 2002-06-12 | Schering Corporation | Combination therapy for eradicating detectable HCV-RNA in antiviral treatment naive patients having chronic hepatitis C infection |
WO1999061055A1 (en) * | 1998-05-22 | 1999-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and therapies based thereon |
ITMI981148A1 (it) * | 1998-05-22 | 1999-11-22 | Therapicon Srl | Utilizzo di lisozima c modificato per preparare composizioni medicinali per il trattamento di alcune gravi malattie |
CA2334267C (en) * | 1998-06-08 | 2009-02-17 | F. Hoffmann-La Roche Ag | Use of peg-ifn-alpha and ribavirin for the treatment of chronic hepatitis c |
US20030143662A1 (en) * | 1998-06-16 | 2003-07-31 | Cummings Richard D. | Glycosulfopeptide inhibitors of leukocyte rolling and methods of use thereof |
EP1087996B1 (en) * | 1998-06-16 | 2007-01-17 | The Board of Regents of The University of Oklahoma | Glycosulfopeptides and methods of synthesis and use thereof |
US7223845B2 (en) | 1998-06-16 | 2007-05-29 | The Board Of Regents Of The University Of Oklahoma | Synthetic glycosulfopeptides and methods of synthesis thereof |
PT1121382E (pt) * | 1998-10-16 | 2006-10-31 | Biogen Idec Inc | Proteinas de fusao do interferao beta e as respectivas utilizacoes |
EP2599503B1 (en) | 1998-10-16 | 2017-05-17 | Biogen MA Inc. | Polymer conjugates of interferon beta-1A and uses thereof |
US6660843B1 (en) * | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
US8288126B2 (en) | 1999-01-14 | 2012-10-16 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
ATE526401T1 (de) | 1999-01-14 | 2011-10-15 | Bolder Biotechnology Inc | Verfahren zur herstellung von proteinen mit freien cysteinresten |
IL144361A0 (en) * | 1999-01-29 | 2002-05-23 | Hoffmann La Roche | Gcsf conjugates |
US6605273B2 (en) | 1999-04-08 | 2003-08-12 | Schering Corporation | Renal cell carcinoma treatment |
TWI292320B (en) | 1999-04-08 | 2008-01-11 | Schering Corp | Melanoma therapy |
US6923966B2 (en) | 1999-04-08 | 2005-08-02 | Schering Corporation | Melanoma therapy |
US6362162B1 (en) | 1999-04-08 | 2002-03-26 | Schering Corporation | CML Therapy |
PE20010288A1 (es) | 1999-07-02 | 2001-03-07 | Hoffmann La Roche | Derivados de eritropoyetina |
ES2364086T3 (es) | 1999-07-07 | 2011-08-24 | Zymogenetics, Inc. | Receptor de citoquina humana. |
WO2001005819A1 (en) * | 1999-07-15 | 2001-01-25 | Kuhnil Pharm. Co., Ltd. | Novel water soluble-cyclosporine conjugated compounds |
US6531122B1 (en) * | 1999-08-27 | 2003-03-11 | Maxygen Aps | Interferon-β variants and conjugates |
US7144574B2 (en) * | 1999-08-27 | 2006-12-05 | Maxygen Aps | Interferon β variants and conjugates |
US7431921B2 (en) * | 2000-04-14 | 2008-10-07 | Maxygen Aps | Interferon beta-like molecules |
AU7684000A (en) | 1999-10-12 | 2001-04-23 | Santen Pharmaceutical Co. Ltd. | Interferon complex and medicinal use thereof |
MXPA02004671A (es) | 1999-11-12 | 2004-09-10 | Maxygen Holdings Ltd | Conjugados de interferon gamma. |
US7230081B1 (en) | 1999-11-12 | 2007-06-12 | Maxygen Holdings, Ltd. | Interferon gamma conjugates |
EP1229924A4 (en) | 1999-11-19 | 2004-12-15 | Univ Leland Stanford Junior | TARGETED BIFUNCTIONAL MOLECULES AND THERAPIES THEREFORE |
US6887842B1 (en) * | 1999-11-19 | 2005-05-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulating a pharmacokinetic property of a drug by administering a bifunctional molecule containing the drug |
US7220552B1 (en) | 1999-11-19 | 2007-05-22 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and their use in the disruption of protein-protein interactions |
EP1234035B1 (en) | 1999-12-03 | 2010-02-24 | ZymoGenetics, Inc. | Human cytokine receptor |
BR0107561A (pt) | 2000-01-10 | 2002-11-19 | Maxygen Holdings Ltd | Polipeptìdios ou conjugados entre polipeptìdios que exibem atividade (g-csf), métodos de preparação dos mesmos e seus usos |
JP2003520247A (ja) * | 2000-01-24 | 2003-07-02 | シェーリング コーポレイション | 癌を処置するためのテモゾロミドとペグ化インターフェロンαとの組み合せ |
EP1908477A3 (en) * | 2000-01-24 | 2008-06-11 | Schering Corporation | Combination of temozolomide and pegylated interferon-alpha for treating cancer |
EP1982732A3 (en) | 2000-02-11 | 2011-06-08 | Bayer HealthCare LLC | Factor VII or VIIA-like conjugates |
KR100353392B1 (ko) * | 2000-03-13 | 2002-09-18 | 선바이오(주) | 높은 생체 활성도를 갖는 생체 활성 단백질과 peg의결합체 제조방법 |
US6777387B2 (en) | 2000-03-31 | 2004-08-17 | Enzon Pharmaceuticals, Inc. | Terminally-branched polymeric linkers containing extension moieties and polymeric conjugates containing the same |
US6756037B2 (en) | 2000-03-31 | 2004-06-29 | Enzon, Inc. | Polymer conjugates of biologically active agents and extension moieties for facilitating conjugation of biologically active agents to polymeric terminal groups |
DE60137525D1 (de) * | 2000-10-16 | 2009-03-12 | Chugai Pharmaceutical Co Ltd | Peg-modifiziertes erythropoietin |
US20020169290A1 (en) * | 2000-11-02 | 2002-11-14 | Claus Bornaes | New multimeric interferon beta polypeptides |
ES2329012T3 (es) | 2000-11-07 | 2009-11-20 | Zymogenetics, Inc. | Receptor del factor de necrosis tumoral humano. |
EP2301971A1 (en) | 2001-02-20 | 2011-03-30 | ZymoGenetics, L.L.C. | Antibodies that bind both BCMA and TACI |
CA2437989A1 (en) * | 2001-02-20 | 2002-08-29 | Enzon, Inc. | Terminally-branched polymeric linkers and polymeric conjugates containing the same |
IL156059A0 (en) | 2001-02-27 | 2003-12-23 | Maxygen Aps | NEW INTERFERON beta-LIKE MOLECULES |
US6875845B2 (en) | 2001-03-02 | 2005-04-05 | Zymogenetics, Inc. | Mouse cytokine receptor |
US7038015B2 (en) * | 2001-04-06 | 2006-05-02 | Maxygen Holdings, Ltd. | Interferon gamma polypeptide variants |
US6958388B2 (en) | 2001-04-06 | 2005-10-25 | Maxygen, Aps | Interferon gamma polypeptide variants |
WO2002083166A1 (fr) * | 2001-04-10 | 2002-10-24 | Santen Pharmaceutical Co., Ltd. | Complexes de polymeres d'interferons et leur utilisation medicinale |
PT1436003E (pt) | 2001-05-24 | 2010-03-12 | Zymogenetics Inc | Proteínas de fusão imunoglobulina taci |
JP4142569B2 (ja) * | 2001-06-22 | 2008-09-03 | 協和醗酵工業株式会社 | 軟膏剤 |
MD2053C2 (ro) * | 2001-07-10 | 2003-07-31 | Национальный Научно-Практический Центр Превентивной Медицины Министерства Здравоохранения Республики Молдова | Remediu cu acţiune interferonogenă |
WO2003018665A1 (en) | 2001-08-22 | 2003-03-06 | Bioartificial Gel Technologies Inc. | Process for the preparation of activated polyethylene glycols |
AU2002346686A1 (en) * | 2001-12-07 | 2003-06-23 | Intermune, Inc. | Compositions and method for treating hepatitis virus infection |
KR100888371B1 (ko) | 2002-01-17 | 2009-03-13 | 동아제약주식회사 | 가지 달린 고분자 유도체와 인터페론 결합체를 포함하는 항바이러스제 |
RS55578B1 (sr) * | 2002-01-18 | 2017-06-30 | Biogen Ma Inc | Polimerna jedinjenja polialkilena i njihova upotreba |
CN1243779C (zh) * | 2002-03-13 | 2006-03-01 | 北京键凯科技有限公司 | 具有y形分支的亲水性聚合物衍生物、其制备方法、与药物分子的结合物以及包含该结合物的药物组合物 |
AU2003223482A1 (en) * | 2002-04-11 | 2003-10-27 | Zymogenetics, Inc. | Use of interleukin-24 to treat ovarian cancer |
BR0309401A (pt) | 2002-04-19 | 2007-02-21 | Zymogenetics Inc | polinucleotìdeo isolado, vetor de expressão, célula cultivada, método para produzir polipeptìdeos, e um anticorpo para um polipeptìdeo, e, anticorpo |
RU2362807C2 (ru) | 2002-06-21 | 2009-07-27 | Ново Нордиск Хелт Кэр Аг | Конъюгат полипептида фактора vii, способ его получения, его применение и содержащая его фармацевтическая композиция |
AU2003239774A1 (en) * | 2002-07-03 | 2004-01-23 | Maxygen Holdings Ltd. | Full-length interferon gamma polypeptide variants |
MXPA05000796A (es) | 2002-07-24 | 2005-04-19 | Hoffmann La Roche | Aditivos de acidos polialquilenglicolicos. |
EP1549332A4 (en) * | 2002-09-05 | 2008-06-18 | Gen Hospital Corp | MODIFIED ASIALO-INTERFERONS AND USES THEREOF |
MXPA05002477A (es) * | 2002-09-05 | 2005-10-19 | Gen Hospital Corp | Asialo-interferones y el tratamiento de cancer de higado. |
JP4237703B2 (ja) * | 2002-09-27 | 2009-03-11 | エフ.ホフマン−ラ ロシュ アーゲー | インスリン様成長因子結合タンパク質−4及びポリ(エチレングリコール)の接合体 |
US20040175359A1 (en) * | 2002-11-12 | 2004-09-09 | Desjarlais John Rudolph | Novel proteins with antiviral, antineoplastic, and/or immunomodulatory activity |
US7314613B2 (en) * | 2002-11-18 | 2008-01-01 | Maxygen, Inc. | Interferon-alpha polypeptides and conjugates |
BR0317742A (pt) * | 2002-12-26 | 2005-11-22 | Mountain View Pharmaceuticals | Conjugados poliméricos de interferon-beta com potência biológica aumentada |
PL396711A1 (pl) * | 2002-12-26 | 2011-12-19 | Mountain View Pharmaceuticals, Inc. | Koniugaty polimerów z cytokinami, chemokinami, czynnikami wzrostu, hormonami polipeptydowymi i ich antagonistami, kompozycja farmaceutyczna i sposób zapobiegania, diagnozowania lub leczenia |
AU2003303519C1 (en) * | 2002-12-31 | 2010-08-12 | Nektar Therapeutics | Polymeric reagents comprising a ketone or a related functional group |
BRPI0407511A (pt) * | 2003-02-19 | 2006-02-14 | Pharmacia Corp | ésteres de polietilenoglicol ativados |
CN1997666A (zh) * | 2003-02-26 | 2007-07-11 | 印特缪恩股份有限公司 | 聚乙二醇修饰的干扰素组合物及其使用方法 |
WO2004078127A2 (en) * | 2003-02-28 | 2004-09-16 | Intermune, Inc. | Continuous delivery methods for treating hepatitis virus infection |
CA2458085A1 (en) | 2003-03-21 | 2004-09-21 | F. Hoffmann-La Roche Ag | Transcriptional activity assay |
WO2005016241A2 (en) | 2003-05-16 | 2005-02-24 | Intermune, Inc. | Synthetic chemokine receptor ligands and methods of use thereof |
ES2303132T3 (es) | 2003-08-07 | 2008-08-01 | Zymogenetics, Inc. | Preparaciones homogeneas de il-29. |
GB0320638D0 (en) | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
CN1867581B (zh) | 2003-10-10 | 2012-02-01 | 诺沃挪第克公司 | Il-21衍生物 |
WO2005037214A2 (en) | 2003-10-14 | 2005-04-28 | Intermune, Inc. | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication |
ES2428358T3 (es) | 2003-10-17 | 2013-11-07 | Novo Nordisk A/S | Terapia de combinación |
WO2005042563A2 (en) * | 2003-10-22 | 2005-05-12 | Akzo Nobel N.V. | Process for incrasing protein pegylation reaction yields by diafiltration ultrafiltration |
WO2005040758A2 (en) * | 2003-10-24 | 2005-05-06 | Intermune, Inc. | Use of pirfenidone in therapeutic regimens |
WO2005062949A2 (en) * | 2003-12-23 | 2005-07-14 | Intermune, Inc. | Method for treating hepatitis virus infection |
GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
US8778880B2 (en) | 2004-02-02 | 2014-07-15 | Ambrx, Inc. | Human growth hormone modified at position 35 |
US7351787B2 (en) * | 2004-03-05 | 2008-04-01 | Bioartificial Gel Technologies, Inc. | Process for the preparation of activated polyethylene glycols |
RU2006145020A (ru) * | 2004-05-19 | 2008-06-27 | Максиджен, Инк. (Us) | Полипептиды и конъюгаты интерферона-альфа |
WO2005123113A2 (en) * | 2004-06-14 | 2005-12-29 | Intermune, Inc. | Interferon compositions and methods of use thereof |
NZ551335A (en) * | 2004-06-18 | 2010-03-26 | Ambrx Inc | Antibodies and fragments thereof comprising an non naturally encoded amino acid coupled to a linker |
BRPI0512396A (pt) * | 2004-07-21 | 2008-03-11 | Ambrx Inc | polipeptìdeos biossintéticos utilizando aminoácidos codificados não naturalmente |
CN101829318B (zh) | 2004-07-29 | 2012-07-04 | 津莫吉尼蒂克斯有限责任公司 | Il-28和il-29治疗癌症和自身免疫性疾病的用途 |
BRPI0513332A (pt) | 2004-08-12 | 2008-05-06 | Schering Corp | formulação de interferon peguilado estável |
US20060204512A1 (en) | 2004-09-23 | 2006-09-14 | Vasgene Therapeutics, Inc. | Polypeptide compounds for inhibiting angiogenesis and tumor growth |
CN103520735B (zh) | 2004-12-22 | 2015-11-25 | Ambrx公司 | 包含非天然编码的氨基酸的人生长激素配方 |
WO2006073846A2 (en) | 2004-12-22 | 2006-07-13 | Ambrx, Inc. | Methods for expression and purification of recombinant human growth hormone |
AU2005319518B2 (en) * | 2004-12-22 | 2010-09-09 | Ambrx, Inc. | Compositions of aminoacyl-tRNA synthetase and uses thereof |
NZ584597A (en) | 2004-12-22 | 2011-09-30 | Ambrx Inc | Modified human growth hormone |
CA2596390A1 (en) | 2005-02-08 | 2006-08-17 | Zymogenetics, Inc. | Anti-il-20, anti-il-22 and anti-il-22ra antibodies and binding partners and methods of using in inflammation |
ATE515512T1 (de) | 2005-05-12 | 2011-07-15 | Zymogenetics Inc | Zusammensetzungen und verfahren zur modulierung von immunreaktionen |
WO2007044083A2 (en) * | 2005-05-18 | 2007-04-19 | Maxygen, Inc. | Evolved interferon-alpha polypeptides |
MX2007015058A (es) * | 2005-06-03 | 2008-01-28 | Ambrx Inc | Moleculas de interferon humano mejoradas y sus usos. |
MX2007015819A (es) * | 2005-06-13 | 2008-02-22 | Nastech Pharm Co | Suministro de derivados peptidicos a traves de la mucosa. |
ATE524183T1 (de) | 2005-06-17 | 2011-09-15 | Novartis Ag | Verwendung von sanglifehrin bei der hcv-therapie |
JP5335422B2 (ja) | 2005-06-17 | 2013-11-06 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 少なくとも1つの非天然のシステインを含んでいる操作されたタンパク質の選択的な還元および誘導体化 |
TW200722104A (en) * | 2005-06-20 | 2007-06-16 | Pepgen Corp | Low-toxicity, long-circulating human interferon-α analogs |
US7695710B2 (en) | 2005-06-20 | 2010-04-13 | Pepgen Corporation | Antitumor and antiviral combination therapies using low-toxicity, long-circulating human interferon-alpha analogs |
US7767799B2 (en) * | 2005-06-29 | 2010-08-03 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | Nucleic acid molecules encoding recombinant interferon-α2 (IFNα2) mutants |
JP5249028B2 (ja) | 2005-07-25 | 2013-07-31 | インターミューン・インコーポレーテッド | C型肝炎ウイルス複製の新規大環状阻害剤 |
DK1937824T3 (da) * | 2005-08-18 | 2013-04-02 | Ambrx Inc | Sammensætninger af tRNA og anvendelser deraf |
BRPI0616589A2 (pt) | 2005-09-28 | 2011-06-28 | Zymogenetics Inc | polipeptìdeo, e, métodos para produzir um anticorpo para um polipeptìdeo, para reduzir ou inibir a inflamação e para tratar um mamìfero afligido com uma doença inflamatória |
DE602006019323D1 (de) | 2005-10-11 | 2011-02-10 | Intermune Inc | Verbindungen und verfahren zur inhibierung der replikation des hepatitis-c-virus |
US20080171696A1 (en) * | 2005-10-21 | 2008-07-17 | Avigenics, Inc. | Pharmacodynamically enhanced therapeutic proteins |
AU2006304856A1 (en) * | 2005-10-21 | 2007-04-26 | Synageva Biopharma Corp. | Glycolated and glycosylated poultry derived therapeutic proteins |
WO2007056448A2 (en) * | 2005-11-08 | 2007-05-18 | Ambrx, Inc. | Accelerants for the modification of non-natural amino acids and non-natural amino acid polypeptides |
ES2547554T3 (es) * | 2005-11-16 | 2015-10-07 | Ambrx, Inc. | Métodos y composiciones que comprenden aminoácidos no naturales |
ES2529065T3 (es) * | 2005-12-14 | 2015-02-16 | Ambrx, Inc. | Composiciones que contienen, procedimientos que implican y usos de aminoácidos no naturales y polipéptidos |
AU2007205545B9 (en) | 2006-01-12 | 2012-10-18 | Hokusan Co. Ltd. | Oral composition containing interferon-alpha |
CN100475270C (zh) | 2006-01-20 | 2009-04-08 | 清华大学 | 一种治疗肿瘤的药物及其应用 |
CN101002945B (zh) | 2006-01-20 | 2012-09-05 | 清华大学 | 一种用于肿瘤治疗的新型复合物 |
MX2008013119A (es) | 2006-04-11 | 2008-10-21 | Novartis Ag | Inhibidores de hcv/vih y sus usos. |
US20080096819A1 (en) * | 2006-05-02 | 2008-04-24 | Allozyne, Inc. | Amino acid substituted molecules |
JP5313129B2 (ja) * | 2006-05-02 | 2013-10-09 | アロザイン, インコーポレイテッド | 非天然アミノ酸置換ポリペプチド |
EP2029738A2 (en) | 2006-05-24 | 2009-03-04 | Novo Nordisk Health Care AG | Factor ix analogues having prolonged in vivo half life |
EP2030628B1 (en) | 2006-06-01 | 2012-08-15 | Yun Cheng | A peptide for preventing or treating liver damage and its derivant and the use |
CN1911447B (zh) * | 2006-06-30 | 2010-05-12 | 复旦大学 | 转铁蛋白-聚乙二醇-药物分子复合物及其制备药物的用途 |
EP1886685A1 (en) | 2006-08-11 | 2008-02-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods, uses and compositions for modulating replication of hcv through the farnesoid x receptor (fxr) activation or inhibition |
EP2054076A2 (en) * | 2006-08-21 | 2009-05-06 | United Therapeutics Corporation | Combination therapy for treatment of viral infections |
EP2069396B1 (en) | 2006-09-08 | 2015-10-21 | Ambrx, Inc. | Modified human plasma polypeptide or fc scaffolds and their uses |
PT2061878E (pt) * | 2006-09-08 | 2014-04-22 | Ambrx Inc | Supressor híbrido arnt para células de vertebrados |
US8420792B2 (en) * | 2006-09-08 | 2013-04-16 | Ambrx, Inc. | Suppressor tRNA transcription in vertebrate cells |
EP2727936B1 (en) | 2006-11-22 | 2016-09-07 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR |
CN101219219B (zh) | 2007-01-10 | 2013-02-13 | 北京普罗吉生物科技发展有限公司 | 包含血管抑素或其片段的复合物、其制备方法及应用 |
ATE516814T1 (de) | 2007-02-02 | 2011-08-15 | Bristol Myers Squibb Co | 10fn3 domain zur behandlung von krankheiten begleitet von unerwünschter angiogenese |
AU2008232937B2 (en) | 2007-03-30 | 2012-09-27 | Ambrx, Inc. | Modified FGF-21 polypeptides and their uses |
EP2076533B1 (en) * | 2007-05-02 | 2014-10-08 | Ambrx, Inc. | Modified interferon beta polypeptides and their uses |
CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
US8597635B2 (en) * | 2007-09-04 | 2013-12-03 | Biosteed Gene Expression Tech. Co., Ltd. | Interferon alpha-2B modified by polyethylene glycol and methods of preparation thereof |
EP2196475B1 (en) | 2007-09-04 | 2012-06-06 | Biosteed Gene Expression Tech. CO., LTD. | INTERFERON ALPHA 2a MODIFIED BY POLYETHYLENE GLYCOL, ITS SYNTHESIS PROCESS AND APPLICATION |
EA201000343A1 (ru) | 2007-10-04 | 2011-10-31 | Займодженетикс, Инк. | ЧЛЕН СЕМЕЙСТВА B7, zB7H6 И РОДСТВЕННЫЕ КОМПОЗИЦИИ И СПОСОБЫ |
JP2011500086A (ja) | 2007-10-22 | 2011-01-06 | シェーリング コーポレイション | 完全ヒト抗vegf抗体および使用方法 |
JP5547083B2 (ja) | 2007-11-20 | 2014-07-09 | アンブルックス,インコーポレイテッド | 修飾されたインスリンポリペプチドおよびそれらの使用 |
CA2708251C (en) | 2007-12-07 | 2016-04-12 | Zymogenetics, Inc. | Humanized antibody molecules specific for il-31 |
NZ602170A (en) | 2008-02-08 | 2014-03-28 | Ambrx Inc | Modified leptin polypeptides and their uses |
CA2720306C (en) | 2008-04-03 | 2016-03-15 | Biosteed Gene Expression Tech. Co., Ltd. | Double-stranded polyethylene glycol modified growth hormone, preparation method and application thereof |
WO2009142773A2 (en) | 2008-05-22 | 2009-11-26 | Bristol-Myers Squibb Company | Multivalent fibronectin based scaffold domain proteins |
EP2313105B1 (en) | 2008-06-27 | 2013-07-24 | ZymoGenetics, Inc. | SOLUBLE HYBRID Fc gamma RECEPTORS AND RELATED METHODS |
NZ600382A (en) * | 2008-07-23 | 2013-11-29 | Ambrx Inc | Modified bovine G-CSF polypeptides and their uses |
MX348657B (es) | 2008-09-26 | 2017-06-21 | Ambrx Inc | Microorganismos y vacunas dependientes de replicacion de aminoacidos no naturales. |
AU2009296397B2 (en) * | 2008-09-26 | 2012-11-08 | Ambrx Inc. | Modified animal erythropoietin polypeptides and their uses |
WO2010039801A2 (en) | 2008-10-02 | 2010-04-08 | The J. David Gladstone Institutes | Methods of treating hepatitis c virus infection |
EP2408449A4 (en) | 2009-03-18 | 2012-08-08 | Univ Leland Stanford Junior | METHODS AND COMPOSITIONS FOR TREATING INFECTION WITH A FLAVIVIRIDAE FAMILY VIRUS |
US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
ES2643446T3 (es) | 2009-06-04 | 2017-11-22 | Novartis Ag | Métodos para la identificación de sitios para conjugación de IgG |
US20110027229A1 (en) | 2009-07-31 | 2011-02-03 | Medtronic, Inc. | Continuous subcutaneous administration of interferon-alpha to hepatitis c infected patients |
AU2010313497B2 (en) | 2009-10-30 | 2013-08-01 | Boehringer Ingelheim International Gmbh | Dosage regimens for HCV combination therapy comprising BI201335, interferon alpha and ribavirin |
SG181769A1 (en) | 2009-12-21 | 2012-07-30 | Ambrx Inc | Modified porcine somatotropin polypeptides and their uses |
CN102753573A (zh) | 2009-12-21 | 2012-10-24 | Ambrx公司 | 经过修饰的牛促生长素多肽和其用途 |
JP2013528374A (ja) | 2010-05-10 | 2013-07-11 | パーシード セラピューティクス リミテッド ライアビリティ カンパニー | Vla4のポリペプチド阻害剤 |
US8765737B1 (en) | 2010-05-11 | 2014-07-01 | Demerx, Inc. | Methods and compositions for preparing and purifying noribogaine |
US8362007B1 (en) | 2010-05-11 | 2013-01-29 | Demerx, Inc. | Substituted noribogaine |
US9394294B2 (en) | 2010-05-11 | 2016-07-19 | Demerx, Inc. | Methods and compositions for preparing and purifying noribogaine |
WO2011150133A2 (en) | 2010-05-26 | 2011-12-01 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
WO2011159930A2 (en) | 2010-06-16 | 2011-12-22 | Medtronic, Inc. | Damping systems for stabilizing medications in drug delivery devices |
US9586954B2 (en) | 2010-06-22 | 2017-03-07 | Demerx, Inc. | N-substituted noribogaine prodrugs |
US8637648B1 (en) | 2010-06-22 | 2014-01-28 | Demerx, Inc. | Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier |
US8741891B1 (en) | 2010-06-22 | 2014-06-03 | Demerx, Inc. | N-substituted noribogaine prodrugs |
US8802832B2 (en) | 2010-06-22 | 2014-08-12 | Demerx, Inc. | Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier |
EP2585065A1 (en) | 2010-06-24 | 2013-05-01 | Panmed Ltd. | Treatment of hepatitis c virus related diseases using hydroxychloroquine or a combination of hydroxychloroquine and an anti-viral agent |
CN103079571A (zh) | 2010-07-23 | 2013-05-01 | 德莫科斯公司 | 降伊波加因碱组合物 |
AU2011291943B2 (en) | 2010-08-17 | 2015-01-22 | Ambrx, Inc. | Modified relaxin polypeptides and their uses |
US9567386B2 (en) | 2010-08-17 | 2017-02-14 | Ambrx, Inc. | Therapeutic uses of modified relaxin polypeptides |
AR083006A1 (es) | 2010-09-23 | 2013-01-23 | Lilly Co Eli | Formulaciones para el factor estimulante de colonias de granulocitos (g-csf) bovino y variantes de las mismas |
WO2012045704A1 (en) | 2010-10-05 | 2012-04-12 | Novartis Ag | New treatments of hepatitis c virus infection |
KR20130120481A (ko) | 2010-10-08 | 2013-11-04 | 노파르티스 아게 | 술파미드 ns3 억제제의 비타민 e 제제 |
CN103221053A (zh) | 2010-11-30 | 2013-07-24 | 诺华有限公司 | 丙型肝炎病毒感染的新疗法 |
EP2481740B1 (en) | 2011-01-26 | 2015-11-04 | DemeRx, Inc. | Methods and compositions for preparing noribogaine from voacangine |
WO2012107589A1 (en) | 2011-02-11 | 2012-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment and prevention of hcv infections |
CN103476409A (zh) | 2011-03-31 | 2013-12-25 | 诺华股份有限公司 | 治疗丙肝病毒感染的阿拉泊韦 |
CA2831675A1 (en) | 2011-04-01 | 2012-10-04 | Novartis Ag | Treatment for infection with hepatitis b virus alone or in combination with hepatitis delta virus and associated liver diseases |
AU2012241859A1 (en) | 2011-04-13 | 2013-10-10 | Debiopharm International Sa | Treatment of Hepatitis C virus infection with alisporivir |
US20140187488A1 (en) | 2011-05-17 | 2014-07-03 | Bristol-Myers Squibb Company | Methods for maintaining pegylation of polypeptides |
WO2012158493A2 (en) | 2011-05-19 | 2012-11-22 | Geysen Hendrik M | Compounds that bind to the erythropoietin receptor |
EP2726502A1 (en) | 2011-07-01 | 2014-05-07 | Bayer Intellectual Property GmbH | Relaxin fusion polypeptides and uses thereof |
US20140314713A1 (en) | 2011-07-20 | 2014-10-23 | Universite Paris Diderot - Paris Vii | Methods for determining treatment response in patients infected with hcv genotype 4 |
JP2014525939A (ja) * | 2011-08-25 | 2014-10-02 | ナノジェン・ファーマシューティカル・バイオテクノロジー | ペグインターフェロンλ1複合体 |
US9617274B1 (en) | 2011-08-26 | 2017-04-11 | Demerx, Inc. | Synthetic noribogaine |
RU2014116988A (ru) | 2011-09-27 | 2015-11-10 | Новартис Аг | Алиспоривир для лечения инфекции, вызванной вирусом гепатита с |
WO2013067029A2 (en) | 2011-10-31 | 2013-05-10 | Bristol-Myers Squibb Company | Fibronectin binding domains with reduced immunogenicity |
SG11201402899TA (en) | 2011-12-06 | 2014-07-30 | Univ Leland Stanford Junior | Methods and compositions for treating viral diseases |
EP2788003A4 (en) | 2011-12-09 | 2015-05-27 | Demerx Inc | PHOSPHATESTER OF NORIBOGAIN |
CA2858820C (en) | 2012-01-25 | 2021-08-17 | Demerx, Inc. | Synthetic voacangine |
US9150584B2 (en) | 2012-01-25 | 2015-10-06 | Demerx, Inc. | Indole and benzofuran fused isoquinuclidene derivatives and processes for preparing them |
US8454947B1 (en) | 2012-03-01 | 2013-06-04 | Nanogen Pharmaceutical Biotechnology | PEG-interferon lambda 1 conjugates |
JP2015509980A (ja) | 2012-03-14 | 2015-04-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Hcv−hiv同時感染患者集団のhcv感染症を治療するための併用療法 |
JP2015512900A (ja) | 2012-03-28 | 2015-04-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 特別な患者の遺伝子亜型分集団のhcv感染症を治療するための併用療法 |
EP2830663B1 (en) | 2012-03-30 | 2019-02-06 | Sorrento Therapeutics Inc. | Fully human antibodies that bind to vegfr2 |
WO2013177187A2 (en) | 2012-05-22 | 2013-11-28 | Massachusetts Institute Of Technology | Synergistic tumor treatment with extended-pk il-2 and therapeutic agents |
WO2013174988A1 (en) | 2012-05-24 | 2013-11-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting and monitoring treatment response in hcv- and hcv/hiv-infected subjects |
EP3553086A1 (en) | 2012-05-31 | 2019-10-16 | Sorrento Therapeutics Inc. | Antigen binding proteins that bind pd-l1 |
CN104583235B (zh) | 2012-06-08 | 2019-03-01 | 苏特罗生物制药公司 | 含位点特异非天然氨基酸残基的抗体、其制备和使用方法 |
CN105050618B (zh) | 2012-06-21 | 2018-11-16 | 索伦托治疗有限公司 | 与c-Met结合的抗原结合蛋白 |
EP2864358B1 (en) | 2012-06-22 | 2019-08-07 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind ccr2 |
ES2611788T3 (es) | 2012-06-26 | 2017-05-10 | Sutro Biopharma, Inc. | Proteínas de Fc modificadas que comprenden residuos de aminoácidos no naturales específicos del sitio, conjugados de las mismas, métodos para su preparación y métodos para su uso |
SG11201501464TA (en) | 2012-08-31 | 2015-03-30 | Sutro Biopharma Inc | Modified amino acids comprising an azido group |
US20140205566A1 (en) | 2012-11-30 | 2014-07-24 | Novartis Ag | Cyclic nucleuoside derivatives and uses thereof |
US8940728B2 (en) | 2012-12-20 | 2015-01-27 | Demerx, Inc. | Substituted noribogaine |
WO2014098877A1 (en) | 2012-12-20 | 2014-06-26 | Demerx, Inc. | Substituted noribogaine |
US9045481B2 (en) | 2012-12-20 | 2015-06-02 | Demerx, Inc. | Substituted noribogaine |
WO2014120891A2 (en) | 2013-02-01 | 2014-08-07 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins |
EP3004169B1 (en) | 2013-05-31 | 2023-03-22 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind pd-1 |
ES2865473T3 (es) | 2013-07-10 | 2021-10-15 | Sutro Biopharma Inc | Anticuerpos que comprenden múltiples residuos de aminoácidos no naturales sitio-específicos, métodos para su preparación y métodos de uso |
WO2015054658A1 (en) | 2013-10-11 | 2015-04-16 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
US11311519B2 (en) | 2014-05-01 | 2022-04-26 | Eiger Biopharmaceuticals, Inc. | Treatment of hepatitis delta virus infection |
PT3137078T (pt) | 2014-05-01 | 2019-06-11 | Eiger Biopharmaceuticals Inc | Tratamento da infeção por vírus da hepatite delta |
US9388239B2 (en) | 2014-05-01 | 2016-07-12 | Consejo Nacional De Investigation Cientifica | Anti-human VEGF antibodies with unusually strong binding affinity to human VEGF-A and cross reactivity to human VEGF-B |
US10076512B2 (en) | 2014-05-01 | 2018-09-18 | Eiger Biopharmaceuticals, Inc. | Treatment of hepatitis delta virus infection |
CA2989550C (en) | 2014-06-18 | 2023-08-08 | Demerx, Inc. | Halogenated indole and benzofuran derivatives of isoquinuclidene and processes for preparing them |
EP3646879B1 (en) | 2014-08-12 | 2024-04-03 | Massachusetts Institute Of Technology | Synergistic tumor treatment with integrin-binding-fc-fusion protein and an immune checkpoint inhibitor |
US20170216403A1 (en) | 2014-08-12 | 2017-08-03 | Massachusetts Institute Of Technology | Synergistic tumor treatment with il-2, a therapeutic antibody, and an immune checkpoint blocker |
CA2958673A1 (en) | 2014-08-22 | 2016-02-25 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind cxcr3 |
US9987241B2 (en) | 2014-09-25 | 2018-06-05 | The Board Of Regents Of The University Of Oklahoma | Enzyme conjugate and prodrug cancer therapy |
JP6702962B2 (ja) | 2014-10-24 | 2020-06-03 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 改変fgf−21ポリペプチドおよびその使用 |
MX2017005244A (es) * | 2014-11-06 | 2017-08-18 | Pharmaessentia Corp | Regimen de dosificacion para interferon pegilado. |
EP3272857B1 (en) * | 2015-03-17 | 2020-08-12 | Shigetaka Shimodaira | Method for preparing dendritic cell by non-adhesive culture using ifn |
WO2016172342A1 (en) | 2015-04-21 | 2016-10-27 | Eiger Biopharmaceuticals, Inc. | Pharmaceutical compositions comprising lonafarnib and ritonavir |
CN108135979A (zh) | 2015-11-03 | 2018-06-08 | 豪夫迈·罗氏有限公司 | Hbv衣壳组装抑制剂和干扰素的组合疗法 |
DK3370723T3 (da) | 2015-11-04 | 2021-01-25 | Eiger Biopharmaceuticals Inc | Behandling af hepatitis delta-virusinfektion |
CN116333124A (zh) | 2016-01-29 | 2023-06-27 | 索伦托药业有限公司 | 与pd-l1结合的抗原结合蛋白 |
WO2018087345A1 (en) | 2016-11-14 | 2018-05-17 | F. Hoffmann-La Roche Ag | COMBINATION THERAPY OF AN HBsAg INHIBITOR, A NUCLEOS(T)IDE ANALOGUE AND AN INTERFERON |
US10350266B2 (en) | 2017-01-10 | 2019-07-16 | Nodus Therapeutics, Inc. | Method of treating cancer with a multiple integrin binding Fc fusion protein |
EP3568150A4 (en) | 2017-01-10 | 2020-12-02 | Xcella Biosciences, Inc. | POLYTHERAPY FOR TUMOR TREATMENT WITH INTEGRIN-BOUND FC FUSION PROTEIN AND IMMUNE MODULATOR |
EP3570849A1 (en) | 2017-01-18 | 2019-11-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment patients suffering from myeloproliferative disorders |
MY193457A (en) | 2017-02-08 | 2022-10-14 | Bristol Myers Squibb Co | Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof |
EP3658173A1 (en) | 2017-07-25 | 2020-06-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating monocytopoiesis |
WO2020032951A1 (en) | 2018-08-09 | 2020-02-13 | The Board Of Regents Of The University Of Oklahoma | Antimalarial enzyme conjugates, kits containing same, and methods of producing and using same |
US11485781B2 (en) | 2017-08-17 | 2022-11-01 | Massachusetts Institute Of Technology | Multiple specificity binders of CXC chemokines |
CN116948006A (zh) | 2018-09-11 | 2023-10-27 | 北京泰德制药股份有限公司 | 白介素-2多肽偶联物及其用途 |
SG11202100935TA (en) | 2018-09-28 | 2021-02-25 | Massachusetts Inst Technology | Collagen-localized immunomodulatory molecules and methods thereof |
AU2019361206A1 (en) | 2018-10-19 | 2021-06-03 | Ambrx, Inc. | Interleukin-10 polypeptide conjugates, dimers thereof, and their uses |
WO2020154032A1 (en) | 2019-01-23 | 2020-07-30 | Massachusetts Institute Of Technology | Combination immunotherapy dosing regimen for immune checkpoint blockade |
KR20210136014A (ko) | 2019-02-12 | 2021-11-16 | 암브룩스, 인코포레이티드 | 항체-tlr 작용제 콘쥬게이트를 함유하는 조성물, 방법 및 이의 용도 |
CN114173784B (zh) | 2019-07-18 | 2023-12-01 | 埃尼奥制药公司 | 降低干扰素的副作用的方法 |
TW202146011A (zh) | 2020-03-05 | 2021-12-16 | 美商詹森藥物公司 | 治療b型肝炎病毒感染之組合療法 |
AU2021233909A1 (en) | 2020-03-11 | 2022-09-29 | Ambrx, Inc. | Interleukin-2 polypeptide conjugates and methods of use thereof |
WO2021228983A1 (en) | 2020-05-13 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A pharmaceutical composition comprising an arsenic compound, an inductor of type-1 ifn and a protein kinase inhibitor for treating cancer |
EP3912627B1 (en) | 2020-05-20 | 2022-09-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the treatment of coronavirus infections |
US20210403908A1 (en) | 2020-06-22 | 2021-12-30 | Janssen Pharmaceuticals, Inc. | Compositions and methods for treatment of hepatitis d virus infection |
AU2021327396A1 (en) | 2020-08-20 | 2023-03-23 | Ambrx, Inc. | Antibody-TLR agonist conjugates, methods and uses thereof |
WO2022043496A2 (en) | 2020-08-28 | 2022-03-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of mait cells as biomarkers and biotargets in covid-19 |
WO2022079205A1 (en) | 2020-10-15 | 2022-04-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of ifn-alpha polypeptides for the treatment of coronavirus infections |
WO2022159414A1 (en) | 2021-01-22 | 2022-07-28 | University Of Rochester | Erythropoietin for gastroinfestinal dysfunction |
KR20240004342A (ko) | 2021-04-03 | 2024-01-11 | 암브룩스, 인코포레이티드 | 항-her2 항체-약물 접합체 및 이의 용도 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
WO1985002572A1 (en) | 1983-12-14 | 1985-06-20 | Fanuc Ltd | Area machining method |
US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4902502A (en) | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
WO1990003133A1 (en) | 1988-09-27 | 1990-04-05 | Sirkka Koistinen | Improvement in table constructions |
US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
Family Cites Families (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2651657A (en) * | 1949-05-21 | 1953-09-08 | Standard Oil Dev Co | Synthetic lubricating oil |
SE337223B (no) * | 1967-05-23 | 1971-08-02 | Pharmacia Ab | |
US3619371A (en) * | 1967-07-03 | 1971-11-09 | Nat Res Dev | Production of a polymeric matrix having a biologically active substance bound thereto |
SE343210B (no) * | 1967-12-20 | 1972-03-06 | Pharmacia Ab | |
DK132327A (no) * | 1968-07-16 | |||
US3632828A (en) * | 1968-12-16 | 1972-01-04 | Dow Chemical Co | Polyethylene glycol monomethyl ether carbonates |
BE758425A (fr) * | 1969-12-02 | 1971-04-16 | Baxter Laboratories Inc | Streptokinase liee chimiquement a une matrice en carbohydrate ( |
DE2247163A1 (de) * | 1972-09-26 | 1974-03-28 | Merck Patent Gmbh | Traegermatrix zur fixierung biologisch wirksamer stoffe und verfahren zu ihrer herstellung |
US4002531A (en) * | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
US4100271A (en) * | 1976-02-26 | 1978-07-11 | Cooper Laboratories, Inc. | Clear, water-miscible, liquid pharmaceutical vehicles and compositions which gel at body temperature for drug delivery to mucous membranes |
GB1578348A (en) * | 1976-08-17 | 1980-11-05 | Pharmacia Ab | Products and a method for the therapeutic suppression of reaginic antibodies responsible for common allergic |
US4094744A (en) * | 1976-11-18 | 1978-06-13 | W. R. Grace & Co. | Water-dispersible protein/polyurethane reaction product |
JPS5470384A (en) * | 1977-08-22 | 1979-06-06 | Inst Obu Kiyansaa Risaachi Roi | High molecular complex |
JPS55110105A (en) * | 1979-02-19 | 1980-08-25 | Japan Atom Energy Res Inst | Preparation of polymer composition containing physiologically active material |
JPS6023084B2 (ja) * | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
US4640835A (en) * | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
EP0098110B1 (en) * | 1982-06-24 | 1989-10-18 | NIHON CHEMICAL RESEARCH KABUSHIKI KAISHA also known as JAPAN CHEMICAL RESEARCH CO., LTD | Long-acting composition |
WO1985003934A1 (en) * | 1984-03-06 | 1985-09-12 | Takeda Chemical Industries, Ltd. | Chemically modified protein and process for its preparation |
US4486344A (en) * | 1983-03-28 | 1984-12-04 | Miles Laboratories, Inc. | Urea-linked immunogens, antibodies, and preparative method |
JPS6098988A (ja) * | 1983-11-01 | 1985-06-01 | Chemo Sero Therapeut Res Inst | Lpf−haの精製法 |
US4496689A (en) * | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
EP0154316B1 (en) * | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
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 |
EP0229108B1 (en) * | 1985-06-26 | 1990-12-27 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4847079A (en) * | 1985-07-29 | 1989-07-11 | Schering Corporation | Biologically stable interferon compositions comprising thimerosal |
US4818769A (en) * | 1985-09-20 | 1989-04-04 | Cetus Corporation | Method of controlling stress-related disease in livestock by administration of human IL-2 |
US5102872A (en) * | 1985-09-20 | 1992-04-07 | Cetus Corporation | Controlled-release formulations of interleukin-2 |
US5100664A (en) * | 1985-09-20 | 1992-03-31 | Cetus Corporation | Human IL-2 as a vaccine adjuvant |
US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
US4810638A (en) * | 1986-07-24 | 1989-03-07 | Miles Inc. | Enzyme-labeled antibody reagent with polyalkyleneglycol linking group |
US4894226A (en) * | 1986-11-14 | 1990-01-16 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polyproline conjugation |
US4851220A (en) * | 1986-11-26 | 1989-07-25 | Schering Corporation | Stable oleaginous gel |
US4871538A (en) * | 1987-07-13 | 1989-10-03 | Schering Corporation | Insoluble copper-alpha interferon complex |
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 |
US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
GB8824591D0 (en) * | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Fractionation process |
AU4660789A (en) * | 1988-11-23 | 1990-06-12 | Genentech Inc. | Polypeptide derivatives |
US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
ES2247656T3 (es) * | 1989-04-19 | 2006-03-01 | Enzon, Inc. | Un proceso para formar un polipeptido modificado que comprende un polipeptido y un oxido de polialquileno. |
ATE136315T1 (de) * | 1989-05-27 | 1996-04-15 | Sumitomo Pharma | Verfahren für die herstellung von polyethylenglykolderivate und modifizierte proteine. |
JP2978187B2 (ja) * | 1989-11-02 | 1999-11-15 | 日本ケミカルリサーチ株式会社 | 修飾スーパーオキサイドディスムターゼの製造法 |
US5234903A (en) * | 1989-11-22 | 1993-08-10 | Enzon, Inc. | Chemically modified hemoglobin as an effective, stable non-immunogenic red blood cell substitute |
US5663141A (en) * | 1989-12-01 | 1997-09-02 | Basf Aktiengesellschaft | Hirudin/polyalkylene glycol conjugates and hirudin muteins |
JPH04202293A (ja) * | 1990-11-29 | 1992-07-23 | Tonen Corp | 作動油 |
US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US5281698A (en) * | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
-
1992
- 1992-08-26 US US07/935,770 patent/US5382657A/en not_active Expired - Lifetime
-
1993
- 1993-08-03 HR HR07/935,770A patent/HRP931094A2/hr not_active Application Discontinuation
- 1993-08-06 SI SI9300423A patent/SI9300423A/sl unknown
- 1993-08-11 CA CA002103829A patent/CA2103829C/en not_active Expired - Lifetime
- 1993-08-13 DK DK93112983T patent/DK0593868T3/da active
- 1993-08-13 EP EP93112983A patent/EP0593868B1/en not_active Expired - Lifetime
- 1993-08-13 ES ES93112983T patent/ES2116376T3/es not_active Expired - Lifetime
- 1993-08-13 AT AT93112983T patent/ATE165102T1/de active
- 1993-08-13 DE DE69317979T patent/DE69317979T2/de not_active Expired - Lifetime
- 1993-08-16 MW MW7693A patent/MW7693A1/xx unknown
- 1993-08-18 HU HU9302366A patent/HUT67013A/hu unknown
- 1993-08-18 CZ CZ931693A patent/CZ169393A3/cs unknown
- 1993-08-19 ZA ZA936098A patent/ZA936098B/xx unknown
- 1993-08-20 NZ NZ264872A patent/NZ264872A/en unknown
- 1993-08-20 SK SK898-93A patent/SK89893A3/sk unknown
- 1993-08-20 NZ NZ248452A patent/NZ248452A/en unknown
- 1993-08-20 IL IL106750A patent/IL106750A0/xx unknown
- 1993-08-20 PH PH46719A patent/PH30460A/en unknown
- 1993-08-20 AU AU44780/93A patent/AU668742B2/en not_active Ceased
- 1993-08-23 BG BG98067A patent/BG98067A/xx unknown
- 1993-08-23 JP JP5229504A patent/JP2859105B2/ja not_active Expired - Lifetime
- 1993-08-23 RO RO93-01141A patent/RO112730B1/ro unknown
- 1993-08-24 UY UY23635A patent/UY23635A1/es unknown
- 1993-08-24 MY MYPI93001695A patent/MY131445A/en unknown
- 1993-08-25 CN CNB971054339A patent/CN1183112C/zh not_active Expired - Lifetime
- 1993-08-25 PL PL93300194A patent/PL300194A1/xx unknown
- 1993-08-25 LV LVP-93-1040A patent/LV10907B/en unknown
- 1993-08-25 CN CN93116479A patent/CN1039015C/zh not_active Expired - Lifetime
- 1993-08-25 YU YU56693A patent/YU56693A/sh unknown
- 1993-08-25 KR KR1019930016550A patent/KR100295520B1/ko not_active IP Right Cessation
- 1993-08-25 LT LTIP888A patent/LT3174B/lt not_active IP Right Cessation
- 1993-08-25 MX MX9305146A patent/MX9305146A/es active IP Right Grant
- 1993-08-25 FI FI933740A patent/FI109765B/fi not_active IP Right Cessation
- 1993-08-25 NO NO933028A patent/NO933028D0/no unknown
- 1993-08-25 IS IS4067A patent/IS4067A/is unknown
- 1993-08-25 BR BR9303469A patent/BR9303469A/pt not_active Application Discontinuation
- 1993-08-26 ZW ZW11193A patent/ZW11193A1/xx unknown
- 1993-08-26 OA OA60405A patent/OA09850A/fr unknown
-
1994
- 1994-11-22 EE EE9400151A patent/EE9400151A/xx unknown
-
1997
- 1997-05-23 CN CNB971054347A patent/CN1155618C/zh not_active Expired - Lifetime
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
WO1985002572A1 (en) | 1983-12-14 | 1985-06-20 | Fanuc Ltd | Area machining method |
US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
WO1990003133A1 (en) | 1988-09-27 | 1990-04-05 | Sirkka Koistinen | Improvement in table constructions |
US4902502A (en) | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
LT3174B (en) | Polyethylene glycol -interferon conjugates | |
EP1496076B1 (en) | Hydrophilic polymer derivate with y type branch and preparation method of it medical composite comprising above compound | |
ES2404685T3 (es) | Derivados heterobifuncionales de poli(etilenglicol) y métodos para su preparación | |
US6436386B1 (en) | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers | |
PL186949B1 (pl) | Fizjologicznie czynny koniugat PEG-IFN-alfa, sposób jego wytwarzania oraz zawierające go kompozycjefarmaceutyczne | |
US20040106747A1 (en) | Polyalkylene glycol acid additives | |
HU211945A9 (en) | Polyethylene glycol protein conjugates | |
CA2679482A1 (en) | Oligomer-protease inhibitor conjugates | |
US7829074B2 (en) | Hydroxypatite-targeting poly(ethylene glycol) and related polymers | |
JP2005514505A (ja) | マルチアーム樹枝状および機能的なpegの調製法および用途 | |
EP1279405A1 (en) | Drugs retained in target tissue over long time | |
CN109589415B (zh) | 一种聚乙二醇-多肽和蛋白类药物的结合物 | |
US20060014666A1 (en) | Targeted hydrophilic polymer, binders with interferon and medical composite comprising above binders | |
EP2440249A2 (en) | Covalent conjugates comprising a protease inhibitor, a water-soluble, non-peptidic oligomer and a lipophilic moiety | |
KR100480432B1 (ko) | G-csf와 폴리에틸렌글리콜 유도체의 배합체 | |
KR100480423B1 (ko) | 에리트로포이에틴과 폴리에틸렌글리콜 유도체의 배합체 | |
AU2014200906A1 (en) | Oligomer-protease inhibitor conjugates |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM9A | Lapsed patents |
Effective date: 19970825 |