DE3586313T2 - Konjugate von pharmazeutisch nuetzlichen proteinen. - Google Patents
Konjugate von pharmazeutisch nuetzlichen proteinen.Info
- Publication number
- DE3586313T2 DE3586313T2 DE8585308533T DE3586313T DE3586313T2 DE 3586313 T2 DE3586313 T2 DE 3586313T2 DE 8585308533 T DE8585308533 T DE 8585308533T DE 3586313 T DE3586313 T DE 3586313T DE 3586313 T2 DE3586313 T2 DE 3586313T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- formula
- protein
- conjugate
- radicals
- 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 - Lifetime
Links
- 102000004169 proteins and genes Human genes 0.000 title claims description 61
- 108090000623 proteins and genes Proteins 0.000 title claims description 61
- 239000003153 chemical reaction reagent Substances 0.000 claims description 20
- 229960005356 urokinase Drugs 0.000 claims description 20
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 19
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 19
- -1 polymethylene Polymers 0.000 claims description 17
- 229920003169 water-soluble polymer Polymers 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 230000002441 reversible effect Effects 0.000 claims description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 10
- 102000010911 Enzyme Precursors Human genes 0.000 claims description 9
- 108010062466 Enzyme Precursors Proteins 0.000 claims description 9
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 8
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000005647 linker group Chemical group 0.000 claims description 8
- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 101710196208 Fibrinolytic enzyme Proteins 0.000 claims description 6
- 125000002723 alicyclic group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229920001281 polyalkylene Polymers 0.000 claims description 6
- 208000007536 Thrombosis Diseases 0.000 claims description 5
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 229920005862 polyol Polymers 0.000 claims description 4
- SRPWOOOHEPICQU-UHFFFAOYSA-N trimellitic anhydride Chemical compound OC(=O)C1=CC=C2C(=O)OC(=O)C2=C1 SRPWOOOHEPICQU-UHFFFAOYSA-N 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- 239000003431 cross linking reagent Substances 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 102000008100 Human Serum Albumin Human genes 0.000 claims 2
- 108091006905 Human Serum Albumin Proteins 0.000 claims 2
- 239000012374 esterification agent Substances 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 description 31
- 229920000642 polymer Polymers 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- 239000000243 solution Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 13
- 230000003480 fibrinolytic effect Effects 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000872 buffer Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 8
- 229920000053 polysorbate 80 Polymers 0.000 description 8
- 239000003527 fibrinolytic agent Substances 0.000 description 7
- 238000002523 gelfiltration Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 229920002684 Sepharose Polymers 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 230000009089 cytolysis Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 108010023197 Streptokinase Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 5
- 229910000397 disodium phosphate Inorganic materials 0.000 description 5
- 235000019800 disodium phosphate Nutrition 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 235000019799 monosodium phosphate Nutrition 0.000 description 5
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 5
- 229910000162 sodium phosphate Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 102000001938 Plasminogen Activators Human genes 0.000 description 4
- 108010001014 Plasminogen Activators Proteins 0.000 description 4
- 229920005654 Sephadex Polymers 0.000 description 4
- 239000012507 Sephadex™ Substances 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 239000003593 chromogenic compound Substances 0.000 description 4
- 230000020176 deacylation Effects 0.000 description 4
- 238000005947 deacylation reaction Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000002427 irreversible effect Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 230000033885 plasminogen activation Effects 0.000 description 4
- 229940127126 plasminogen activator Drugs 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 238000011088 calibration curve Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 150000002148 esters Chemical group 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 108010082974 polysarcosine Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 3
- 229940048086 sodium pyrophosphate Drugs 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 3
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000012062 aqueous buffer Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- TUHVEAJXIMEOSA-UHFFFAOYSA-N gamma-guanidinobutyric acid Natural products NC(=[NH2+])NCCCC([O-])=O TUHVEAJXIMEOSA-UHFFFAOYSA-N 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229960002897 heparin Drugs 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
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 229960005202 streptokinase Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- APIBROGXENTUGB-ZUQRMPMESA-M triphenyl-[(e)-3-phenylprop-2-enyl]phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C\C=C\C1=CC=CC=C1 APIBROGXENTUGB-ZUQRMPMESA-M 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 229940038773 trisodium citrate Drugs 0.000 description 2
- MFGALGYVFGDXIX-UHFFFAOYSA-N 2,3-Dimethylmaleic anhydride Chemical compound CC1=C(C)C(=O)OC1=O MFGALGYVFGDXIX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000027219 Deficiency disease Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108010058861 Fibrin Fibrinogen Degradation Products Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 102000009127 Glutaminase Human genes 0.000 description 1
- 108010073324 Glutaminase Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 102000016871 Hexosaminidase A Human genes 0.000 description 1
- 108010053317 Hexosaminidase A Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 238000000023 Kugelrohr distillation Methods 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 229910018487 Ni—Cr Inorganic materials 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 108010092464 Urate Oxidase Proteins 0.000 description 1
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 229940074608 allergen extract Drugs 0.000 description 1
- 229960004784 allergens Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- VNNRSPGTAMTISX-UHFFFAOYSA-N chromium nickel Chemical compound [Cr].[Ni] VNNRSPGTAMTISX-UHFFFAOYSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 239000003085 diluting agent 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
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 125000001033 ether group Chemical group 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
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000208 fibrin degradation product Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 108010087750 lysyl-plasminogen Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940048084 pyrophosphate Drugs 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- HHLJUSLZGFYWKW-UHFFFAOYSA-N triethanolamine hydrochloride Chemical compound Cl.OCCN(CCO)CCO HHLJUSLZGFYWKW-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB848430252A GB8430252D0 (en) | 1984-11-30 | 1984-11-30 | Compounds |
Publications (2)
Publication Number | Publication Date |
---|---|
DE3586313D1 DE3586313D1 (de) | 1992-08-13 |
DE3586313T2 true DE3586313T2 (de) | 1993-01-21 |
Family
ID=10570497
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE8585308533T Expired - Lifetime DE3586313T2 (de) | 1984-11-30 | 1985-11-25 | Konjugate von pharmazeutisch nuetzlichen proteinen. |
Country Status (9)
Families Citing this family (131)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4842868A (en) * | 1986-09-26 | 1989-06-27 | Helwing Robert F | Covalently bonded active agents with carbonium ion base groups |
US5214132A (en) * | 1986-12-23 | 1993-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Polypeptide derivatives of human granulocyte colony stimulating factor |
IE64284B1 (en) * | 1987-08-03 | 1995-07-26 | Ddi Pharmaceuticals | Conjugates of superoxide dismutase |
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 |
JPH079429B2 (ja) * | 1988-10-12 | 1995-02-01 | 財団法人化学及血清療法研究所 | 人工担体およびその製造方法 |
US5091176A (en) * | 1988-11-02 | 1992-02-25 | W. R. Grace & Co.-Conn. | Polymer-modified peptide drugs having enhanced biological and pharmacological activities |
US5162430A (en) * | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
US5510418A (en) * | 1988-11-21 | 1996-04-23 | Collagen Corporation | Glycosaminoglycan-synthetic polymer conjugates |
US5306500A (en) * | 1988-11-21 | 1994-04-26 | Collagen Corporation | Method of augmenting tissue with collagen-polymer conjugates |
US5565519A (en) * | 1988-11-21 | 1996-10-15 | Collagen Corporation | Clear, chemically modified collagen-synthetic polymer conjugates for ophthalmic applications |
EP0395918A3 (en) * | 1989-04-13 | 1991-10-23 | Vascular Laboratory, Inc. | Plasminogen activator complex of pure pro-urokinase covalently bound by a disulfide bridge to human serum albumin |
US5334379A (en) * | 1989-07-14 | 1994-08-02 | American Cyanamid Company | Cytokine and hormone carriers for conjugate vaccines |
US5767072A (en) * | 1989-09-14 | 1998-06-16 | Board Of Regents, The University Of Texas System | Therapeutic compositions comprising a CD4 peptide and methods of treatment of HIV infections |
IE912365A1 (en) * | 1990-07-23 | 1992-01-29 | Zeneca Ltd | Continuous release pharmaceutical compositions |
US5595732A (en) * | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
ATE367827T1 (de) | 1992-11-16 | 2007-08-15 | Centocor Inc | Verfahren zur reduzierung der immunogenizität der variablen regionen von antikörpern |
DE69331805T2 (de) * | 1992-12-10 | 2002-11-28 | Enzon, Inc. | Glycolipid enzym-polymer konjugate |
US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
HUT75533A (en) * | 1993-11-10 | 1997-05-28 | Schering Corp | Improved interferon polymer conjugates |
US6458762B1 (en) | 1994-03-28 | 2002-10-01 | Baxter International, Inc. | Therapeutic use of hemoglobin for preserving tissue viability and reducing restenosis |
EP0773975A4 (en) * | 1994-08-04 | 1998-06-10 | Gordon George Wallace | CONDUCTIVE ELECTROACTIVE BIOMATERIALS |
US5738846A (en) * | 1994-11-10 | 1998-04-14 | Enzon, Inc. | Interferon polymer conjugates and process for preparing the same |
US5770577A (en) * | 1994-11-14 | 1998-06-23 | Amgen Inc. | BDNF and NT-3 polypeptides selectively linked to polyethylene glycol |
CN1168694A (zh) * | 1994-12-07 | 1997-12-24 | 诺沃挪第克公司 | 具有减弱的变应原性的多肽 |
US5695760A (en) * | 1995-04-24 | 1997-12-09 | Boehringer Inglehiem Pharmaceuticals, Inc. | Modified anti-ICAM-1 antibodies and their use in the treatment of inflammation |
US6428790B1 (en) * | 1995-04-27 | 2002-08-06 | The United States Of America As Represented By The Secretary Department Of Health And Human Services | Cyanovirin conjugates and matrix-anchored cyanovirin and related compositions and methods of use |
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 |
ATE330644T1 (de) * | 1995-12-18 | 2006-07-15 | Angiotech Biomaterials Corp | Vernetzten polymerisatmassen und verfahren für ihre verwendung |
US6833408B2 (en) * | 1995-12-18 | 2004-12-21 | Cohesion Technologies, Inc. | Methods for tissue repair using adhesive materials |
BR9510676A (pt) * | 1995-12-29 | 1999-11-23 | Procter & Gamble | Composições detergentes compreendendo enzinas imobilizadas |
EP0894128A1 (en) * | 1996-02-15 | 1999-02-03 | Novo Nordisk A/S | Conjugation of polypeptides |
US6106828A (en) * | 1996-02-15 | 2000-08-22 | Novo Nordisk A/S | Conjugation of polypeptides |
TW517067B (en) * | 1996-05-31 | 2003-01-11 | Hoffmann La Roche | Interferon conjugates |
EP0932390A1 (en) * | 1996-10-11 | 1999-08-04 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method |
US6416756B1 (en) | 1997-01-10 | 2002-07-09 | Novozymes A/S | Modified protease having 5 to 13 covalently coupled polymeric molecules for skin care |
JPH10276776A (ja) * | 1997-04-07 | 1998-10-20 | Toyobo Co Ltd | 可逆的に不活化された耐熱性dnaポリメラーゼ |
WO1999058651A1 (en) * | 1998-05-08 | 1999-11-18 | University Of Southern California | Size enhanced fibrinolytic enzymes |
EP1087778B1 (en) * | 1998-06-08 | 2005-10-26 | F. Hoffmann-La Roche Ag | Use of peg-ifn-alpha and ribavirin for the treatment of chronic hepatitis c |
US6461849B1 (en) | 1998-10-13 | 2002-10-08 | Novozymes, A/S | Modified polypeptide |
TWI242000B (en) * | 1998-12-10 | 2005-10-21 | Univ Southern California | Reversible aqueous pH sensitive lipidizing reagents, compositions and methods of use |
US7112337B2 (en) | 1999-04-23 | 2006-09-26 | Alza Corporation | Liposome composition for delivery of nucleic acid |
US7303760B2 (en) * | 1999-04-23 | 2007-12-04 | Alza Corporation | Method for treating multi-drug resistant tumors |
CN1244376C (zh) | 1999-04-23 | 2006-03-08 | 阿尔萨公司 | 可释放的键和含有该键的组合物 |
US7238368B2 (en) * | 1999-04-23 | 2007-07-03 | Alza Corporation | Releasable linkage and compositions containing same |
EP1198565A1 (en) * | 1999-07-07 | 2002-04-24 | Maxygen Aps | A method for preparing modified polypeptides |
US6423666B1 (en) | 1999-10-05 | 2002-07-23 | Bio-Rad Laboratories, Inc. | Large-pore chromatographic beads prepared by suspension polymerization |
US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
WO2001051510A2 (en) | 2000-01-10 | 2001-07-19 | Maxygen Holdings Ltd | G-csf conjugates |
CA2739933A1 (en) | 2000-02-11 | 2001-08-16 | Bayer Healthcare Llc | Factor vii or viia-like molecules |
US7829074B2 (en) * | 2001-10-18 | 2010-11-09 | Nektar Therapeutics | Hydroxypatite-targeting poly(ethylene glycol) and related polymers |
US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
MXPA03007619A (es) | 2001-02-27 | 2003-12-04 | Maxygen Aps | Nuevas moleculas similares a interferon beta. |
GB0123232D0 (en) * | 2001-09-26 | 2001-11-21 | Smith & Nephew | Polymers |
IL161051A0 (en) | 2001-10-02 | 2004-08-31 | Genentech Inc | Apo-2 ligand variants and uses thereof |
AU2003240439B2 (en) | 2002-06-21 | 2009-05-21 | Novo Nordisk Health Care Ag | Pegylated factor VII glycoforms |
AU2003247609A1 (en) | 2002-06-24 | 2004-01-06 | Genentech, Inc. | Apo-2 ligand/trail variants and uses thereof |
AU2003285200A1 (en) * | 2002-11-09 | 2004-06-03 | Nobex Corporation | Modified carbamate-containing prodrugs and methods of synthesizing same |
DE60331367D1 (de) | 2002-12-30 | 2010-04-01 | Angiotech Int Ag | Wirkstofffreisetzung von schnell gelierender polymerzusammensetzung |
US20040219214A1 (en) * | 2002-12-30 | 2004-11-04 | Angiotech International Ag | Tissue reactive compounds and compositions and uses thereof |
US20040151766A1 (en) * | 2003-01-30 | 2004-08-05 | Monahan Sean D. | Protein and peptide delivery to mammalian cells in vitro |
GB0305989D0 (en) * | 2003-03-15 | 2003-04-23 | Delta Biotechnology Ltd | Agent |
CN1867581B (zh) | 2003-10-10 | 2012-02-01 | 诺沃挪第克公司 | Il-21衍生物 |
EP2633866A3 (en) | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
JP2007519422A (ja) | 2004-02-02 | 2007-07-19 | アンブレツクス・インコーポレイテツド | 修飾されたヒト四螺旋バンドルポリペプチド及びそれらの使用 |
US20100028995A1 (en) * | 2004-02-23 | 2010-02-04 | Anaphore, Inc. | Tetranectin Trimerizing Polypeptides |
AU2005238015A1 (en) * | 2004-04-21 | 2005-11-10 | Alza Corporation | Polymer conjugate releasable under mild thiolytic conditions |
BRPI0510477B1 (pt) | 2004-04-28 | 2023-01-17 | Angiotech Biomaterials Corporation | Método para formar um gel e dispositivo para uso em aplicações médicas |
JP2008503217A (ja) | 2004-06-18 | 2008-02-07 | アンブレツクス・インコーポレイテツド | 新規抗原結合ポリペプチド及びそれらの使用 |
CA2569381A1 (en) | 2004-07-21 | 2006-08-31 | Ambrx, Inc. | Biosynthetic polypeptides utilizing non-naturally encoded amino acids |
CA2581093C (en) | 2004-09-17 | 2014-11-18 | Angiotech Biomaterials Corporation | Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use |
EP1836314B1 (en) | 2004-12-22 | 2012-01-25 | Ambrx, Inc. | Modified human growth hormone |
US20060188498A1 (en) | 2005-02-18 | 2006-08-24 | Genentech, Inc. | Methods of using death receptor agonists and EGFR inhibitors |
EP1893632B1 (en) | 2005-06-17 | 2015-08-12 | Novo Nordisk Health Care AG | Selective reduction and derivatization of engineered factor vii proteins comprising at least one non-native cysteine |
CN101454461A (zh) | 2005-11-16 | 2009-06-10 | Ambrx公司 | 包括非天然氨基酸的方法和组合物 |
CN101484576A (zh) | 2006-05-24 | 2009-07-15 | 诺沃-诺迪斯克保健股份有限公司 | 具有延长的体内半寿期的因子ix类似物 |
AU2007292903B2 (en) | 2006-09-08 | 2012-03-29 | Ambrx, Inc. | Modified human plasma polypeptide or Fc scaffolds and their uses |
JP2010508271A (ja) | 2006-10-27 | 2010-03-18 | ウェイ‐チャン シェン | 脂質化インターフェロンおよびその使用 |
AU2008232937B2 (en) | 2007-03-30 | 2012-09-27 | Ambrx, Inc. | Modified FGF-21 polypeptides and their uses |
WO2009036349A1 (en) * | 2007-09-12 | 2009-03-19 | Anaphore, Inc. | Hsp70-based treatment for autoimmune diseases |
KR101644658B1 (ko) | 2007-10-23 | 2016-08-01 | 넥타르 테라퓨틱스 | 하이드록시아파타이트-표적 다중팔 중합체 및 그로부터 제조된 컨쥬게이트 |
JP2011502520A (ja) * | 2007-11-09 | 2011-01-27 | アナフォア インコーポレイテッド | 疾患治療のためのマンノース結合レクチンの融合タンパク質 |
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 |
US9938333B2 (en) | 2008-02-08 | 2018-04-10 | Ambrx, Inc. | Modified leptin polypeptides and their uses |
EA019968B1 (ru) | 2008-07-23 | 2014-07-30 | Амбркс, Инк. | Модифицированные бычьи полипептиды g-csf и их применение |
NO2337846T3 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2008-09-26 | 2018-06-16 | ||
PT2342223T (pt) | 2008-09-26 | 2017-07-07 | Lilly Co Eli | Polipéptidos de eritropoetina animal modificados e suas utilizações |
US20100105620A1 (en) * | 2008-10-10 | 2010-04-29 | Anaphore, Inc. | Polypeptides that bind Trail-R1 and Trail-R2 |
WO2010080720A2 (en) * | 2009-01-12 | 2010-07-15 | Nektar Therapeutics | Conjugates of a lysosomal enzyme moiety and a water soluble polymer |
US20110086806A1 (en) * | 2009-10-09 | 2011-04-14 | Anaphore, Inc. | Polypeptides that Bind IL-23R |
US20110086770A1 (en) * | 2009-10-09 | 2011-04-14 | Anaphore, Inc. | Combinatorial Libraries Based on C-type Lectin-like Domain |
EA201290542A1 (ru) | 2009-12-21 | 2013-07-30 | Амбркс, Инк. | Модифицированные свиные соматотропиновые полипептиды и их применение |
EP2805964A1 (en) | 2009-12-21 | 2014-11-26 | Ambrx, Inc. | Modified bovine somatotropin polypeptides and their uses |
AU2011222883B2 (en) | 2010-03-05 | 2016-05-26 | Omeros Corporation | Chimeric inhibitor molecules of complement activation |
WO2011143274A1 (en) | 2010-05-10 | 2011-11-17 | Perseid Therapeutics | Polypeptide inhibitors of vla4 |
SMT201900495T1 (it) | 2010-08-17 | 2019-11-13 | Ambrx Inc | Polipeptidi di relaxina modificati e loro usi |
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 |
CA2834776A1 (en) | 2011-05-03 | 2012-11-08 | Genentech, Inc. | Therapeutic apo2l/trail polypeptides and death receptor agonist antibodies |
BR112014000055A2 (pt) | 2011-07-01 | 2017-06-13 | Bayer Ip Gmbh | polipeptídeos de fusão de relaxina e usos dos mesmos |
GB201117428D0 (en) * | 2011-10-07 | 2011-11-23 | Bicycle Therapeutics Ltd | Structured polypeptides with sarcosine linkers |
EP2606884A1 (en) | 2011-12-21 | 2013-06-26 | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Inhibitors of notch signaling pathway and use thereof in treatment of cancers |
EP3505534A1 (en) | 2012-06-08 | 2019-07-03 | Sutro Biopharma, Inc. | Antibodies comprising sitespecific nonnatural amino acid residues, methods of their preparation and methods of their use |
EP3135690A1 (en) | 2012-06-26 | 2017-03-01 | Sutro Biopharma, Inc. | Modified fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use |
DK2890402T3 (da) | 2012-08-31 | 2019-07-15 | Sutro Biopharma Inc | Modificerede aminosyrer omfattende en azidogruppe |
US9764039B2 (en) | 2013-07-10 | 2017-09-19 | Sutro Biopharma, Inc. | Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use |
WO2015023596A1 (en) | 2013-08-12 | 2015-02-19 | Genentech, Inc. | Compositions and method for treating complement-associated conditions |
US9840493B2 (en) | 2013-10-11 | 2017-12-12 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
US10179821B2 (en) | 2014-05-01 | 2019-01-15 | Genentech, Inc. | Anti-factor D antibodies |
BR112017008157A2 (pt) | 2014-10-24 | 2017-12-19 | Bristol Myers Squibb Co | polipeptídeos de fgf-21 modificados e usos dos mesmos |
EP3307326B9 (en) | 2015-06-15 | 2021-02-24 | Angiochem Inc. | Methods for the treatment of leptomeningeal carcinomatosis |
US10407510B2 (en) | 2015-10-30 | 2019-09-10 | Genentech, Inc. | Anti-factor D antibodies and conjugates |
US10654932B2 (en) | 2015-10-30 | 2020-05-19 | Genentech, Inc. | Anti-factor D antibody variant conjugates and uses thereof |
US11617799B2 (en) | 2016-06-27 | 2023-04-04 | Tagworks Pharmaceuticals B.V. | Cleavable tetrazine used in bio-orthogonal drug activation |
AU2018219283B2 (en) | 2017-02-08 | 2022-05-19 | Bristol-Myers Squibb Company | Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof |
JP2021528444A (ja) | 2018-06-21 | 2021-10-21 | セレスティア バイオテック アーゲー | アミノジアリールエーテル及びアミノジアリールエーテル塩酸塩の製造方法 |
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 |
EP3867265A1 (en) | 2018-10-19 | 2021-08-25 | Ambrx, Inc. | Interleukin-10 polypeptide conjugates, dimers thereof, and their uses |
CN119455004A (zh) | 2019-02-12 | 2025-02-18 | Ambrx公司 | 包含抗体-tlr激动剂缀合物的组合物、方法和用途 |
WO2020208139A1 (en) | 2019-04-10 | 2020-10-15 | Cellestia Biotech Ag | Inhibitors of notch signalling pathway and use thereof in treatment of cancers |
AU2021233909A1 (en) | 2020-03-11 | 2022-09-29 | Ambrx, Inc. | Interleukin-2 polypeptide conjugates and methods of use thereof |
MX2022011752A (es) | 2020-03-24 | 2022-10-18 | Genentech Inc | Agentes de fijacion a tie2 y metodos de uso. |
JP2023538071A (ja) | 2020-08-20 | 2023-09-06 | アンブルックス,インコーポレイテッド | 抗体-tlrアゴニストコンジュゲート、その方法及び使用 |
US20240041884A1 (en) | 2020-12-07 | 2024-02-08 | Cellestia Biotech Ag | Pharmaceutical Combinations for Treating Cancer |
EP4008324A1 (en) | 2020-12-07 | 2022-06-08 | Cellestia Biotech AG | Combinations comprising an inhibitor of an anti-apoptotic protein, such as bcl-2, bcl-xl, bclw or mcl-1, and a notch signaling pathway inhibitor for treating cancer |
CN112451681B (zh) * | 2020-12-09 | 2023-08-25 | 苏州大学 | 酸敏感型聚合物-药物偶联物及其制备和应用 |
JP2024512775A (ja) | 2021-04-03 | 2024-03-19 | アンブルックス,インコーポレイテッド | 抗her2抗体薬物コンジュゲート及びその使用 |
WO2022253794A2 (en) | 2021-06-02 | 2022-12-08 | Cellestia Biotech Ag | Method for treating an autoimmune and inflammatory disease |
US20250000870A1 (en) | 2021-11-08 | 2025-01-02 | Cellestia Biotech Ag | Pharmaceutical Combinations for Treating Cancer |
EP4223292A1 (en) | 2022-02-07 | 2023-08-09 | Cellestia Biotech AG | Pharmaceutical combinations for treating cancer |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3499007A (en) * | 1964-12-05 | 1970-03-03 | Cassella Farbwerke Mainkur Ag | Addition products of maleic anhydride to polyalkylene ethers |
GB1390716A (en) * | 1972-06-27 | 1975-04-16 | Mitsubishi Electric Corp | Ester of trimellitic anhydride and process for producing the same |
GB1479268A (en) * | 1973-07-05 | 1977-07-13 | Beecham Group Ltd | Pharmaceutical compositions |
US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
EP0038154B1 (en) * | 1980-04-15 | 1983-09-21 | Beecham Group Plc | Allergens modified with polysarcosines |
US4640835A (en) * | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
JPS5896026A (ja) * | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 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 |
JPS58225025A (ja) * | 1982-06-24 | 1983-12-27 | Nippon Chem Res Kk | 効力持続性組成物 |
JPS5959629A (ja) * | 1982-09-27 | 1984-04-05 | Nippon Chem Res Kk | 効力持続性組成物 |
US4609546A (en) * | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
US4496689A (en) * | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
US4764368A (en) * | 1984-08-29 | 1988-08-16 | Dana-Farber Cancer Institute, Inc. | Acid-cleavable compound |
US4542225A (en) * | 1984-08-29 | 1985-09-17 | Dana-Farber Cancer Institute, Inc. | Acid-cleavable compound |
US4863735A (en) * | 1985-02-19 | 1989-09-05 | Massachusetts Institute Of Technology | Biodegradable polymeric drug delivery system with adjuvant activity |
US4859736A (en) * | 1987-03-30 | 1989-08-22 | Ciba-Geigy Corporation | Synthetic polystyrene resin and its use in solid phase peptide synthesis |
-
1984
- 1984-11-30 GB GB848430252A patent/GB8430252D0/en active Pending
-
1985
- 1985-11-25 DE DE8585308533T patent/DE3586313T2/de not_active Expired - Lifetime
- 1985-11-25 EP EP85308533A patent/EP0183503B1/en not_active Expired - Lifetime
- 1985-11-27 US US07/802,663 patent/US4935465A/en not_active Expired - Lifetime
- 1985-11-28 DK DK552285A patent/DK552285A/da not_active Application Discontinuation
- 1985-11-28 AU AU50445/85A patent/AU5044585A/en not_active Abandoned
- 1985-11-29 GR GR852877A patent/GR852877B/el unknown
- 1985-11-29 PT PT81581A patent/PT81581B/pt unknown
- 1985-11-29 JP JP60269206A patent/JPH0717517B2/ja not_active Expired - Fee Related
-
1994
- 1994-01-27 JP JP6023584A patent/JP2545339B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
JP2545339B2 (ja) | 1996-10-16 |
JPH06279318A (ja) | 1994-10-04 |
PT81581A (en) | 1985-12-01 |
JPS61155333A (ja) | 1986-07-15 |
DK552285D0 (da) | 1985-11-28 |
GR852877B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1986-03-31 |
DE3586313D1 (de) | 1992-08-13 |
JPH0717517B2 (ja) | 1995-03-01 |
AU5044585A (en) | 1986-07-17 |
EP0183503A2 (en) | 1986-06-04 |
GB8430252D0 (en) | 1985-01-09 |
EP0183503A3 (en) | 1988-01-07 |
US4935465A (en) | 1990-06-19 |
EP0183503B1 (en) | 1992-07-08 |
DK552285A (da) | 1986-05-31 |
PT81581B (en) | 1987-07-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE3586313T2 (de) | Konjugate von pharmazeutisch nuetzlichen proteinen. | |
EP0306824B1 (de) | Stabilisierte Humanprotein-Präparate | |
DE60036017T2 (de) | Verfahren zur thrombolyse durch lokale behandlung mit reversibel inaktiviertem, angesäuertem plasmin | |
DE69828330T2 (de) | Aktiviertes Protein C Formulierungen | |
DE3689943T2 (de) | Degradierte Spezies eines Gewebeplasminogenaktivators, pharmazeutische Zubereitung und Verfahren zur Herstellung derselben. | |
DE3780218T2 (de) | Tumor-nekrose-faktor-formulierung und ihre herstellung. | |
DE69433133T2 (de) | Lösliches thrombomodulin enthaltende zubereitung | |
DE69434448T2 (de) | Polymer-peptid konjugate | |
DE3240174C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
EP0382174B1 (de) | Gewebs-Plasminogenaktivator-Derivat | |
DE60109625T3 (de) | Flüssige arzneizubereitung enthaltend ein erythropoietin derivat | |
DE69625085T2 (de) | Konjugate eines polypeptids und eines biologisch verträglichem polymer | |
DE69015182T2 (de) | Thrombus-gerichtete komplexe, die aus plasminogenaktivator und fibrinfragmenten zusammengesetzt sind. | |
AT391812B (de) | Verfahren zur herstellung einer parenteralen t-pa-loesung | |
DE3486341T2 (de) | Derivate von Dextran mit antikoagulierenden und antikomplementären Eigenschaften, ihre Herstellung und ihre biologischen Anwendungen. | |
DE3617752C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
EP0765669A1 (de) | Pharmazeutische Zusammensetzung zur Behandlung von Blutgerinnungsstörungen, Verfahren zur Herstellung derselben und deren Verwendung | |
DE4411143C2 (de) | Thrombosemittel | |
DE3486029T2 (de) | Ifn-praeparat mit verzoegerter abgabe fuer parentale verabreichung. | |
CH616942A5 (en) | Method for suppressing the immunogenic action of a biocatalyst. | |
EP1572229A2 (de) | Stabile therapeutische proteine | |
CH637992A5 (de) | Verfahren zur herstellung eines komplexes aus streptokinase und einer leichten (b) plasmin-kettenfraktion mit einem aktiven serinprotease-zentrum. | |
JPH0567278B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
EP0361475A1 (de) | Präparat von in Prokaryonten exprimiertem Plasminogenaktivator | |
DE69930419T2 (de) | Verwendung von menschliche protein c zur herstellung eines arzneimittels zur behandlung von heparininduzierter thrombozytopenie |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
8364 | No opposition during term of opposition | ||
8327 | Change in the person/name/address of the patent owner |
Owner name: SMITHKLINE BEECHAM PLC, BRENTFORD, MIDDLESEX, GB |
|
8327 | Change in the person/name/address of the patent owner |
Owner name: ADPROTECH PLC, ROYSTON, HERTFORDSHIRE, GB |
|
8327 | Change in the person/name/address of the patent owner |
Owner name: ADPROTECH LTD., ROYSTON, HERTFORDSHIRE, GB |