KR101486449B1 - 다작용성 형태의 폴리옥시졸린 공중합체 및 이를 포함하는 약물 조성물 - Google Patents
다작용성 형태의 폴리옥시졸린 공중합체 및 이를 포함하는 약물 조성물 Download PDFInfo
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- KR101486449B1 KR101486449B1 KR1020107017208A KR20107017208A KR101486449B1 KR 101486449 B1 KR101486449 B1 KR 101486449B1 KR 1020107017208 A KR1020107017208 A KR 1020107017208A KR 20107017208 A KR20107017208 A KR 20107017208A KR 101486449 B1 KR101486449 B1 KR 101486449B1
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- polyoxazoline
- unsubstituted
- rti
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- 229920000765 poly(2-oxazolines) Polymers 0.000 title claims description 114
- 239000000203 mixture Substances 0.000 title abstract description 54
- 239000003814 drug Substances 0.000 title abstract description 8
- 229940079593 drug Drugs 0.000 title description 2
- 125000000524 functional group Chemical group 0.000 claims abstract description 132
- -1 2-substituted 2-oxazolines Chemical class 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 27
- 229920005604 random copolymer Polymers 0.000 claims abstract description 14
- 229920001400 block copolymer Polymers 0.000 claims abstract description 11
- 230000008685 targeting Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 150000001412 amines Chemical class 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 150000001735 carboxylic acids Chemical class 0.000 claims description 17
- 125000005647 linker group Chemical group 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 16
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 14
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 150000001299 aldehydes Chemical class 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 150000001298 alcohols Chemical class 0.000 claims description 10
- 150000001345 alkine derivatives Chemical class 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 10
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 9
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 8
- 230000000977 initiatory effect Effects 0.000 claims description 7
- 150000001540 azides Chemical class 0.000 claims description 6
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical class ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 150000003457 sulfones Chemical class 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 150000003923 2,5-pyrrolediones Chemical class 0.000 claims 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical class O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims 2
- 150000002019 disulfides Chemical class 0.000 claims 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 229920005862 polyol Polymers 0.000 claims 1
- 150000003077 polyols Chemical class 0.000 claims 1
- 229920000642 polymer Polymers 0.000 abstract description 49
- 229920001577 copolymer Polymers 0.000 abstract description 6
- 229940124597 therapeutic agent Drugs 0.000 abstract description 4
- 229940039227 diagnostic agent Drugs 0.000 abstract description 3
- 239000000032 diagnostic agent Substances 0.000 abstract description 3
- 230000001268 conjugating effect Effects 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 33
- 125000000623 heterocyclic group Chemical group 0.000 description 28
- 238000006116 polymerization reaction Methods 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 24
- 239000000843 powder Substances 0.000 description 18
- 229910052799 carbon Inorganic materials 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 125000004434 sulfur atom Chemical group 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 239000000178 monomer Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 125000004430 oxygen atom Chemical group O* 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 description 11
- NYEZZYQZRQDLEH-UHFFFAOYSA-N 2-ethyl-4,5-dihydro-1,3-oxazole Chemical compound CCC1=NCCO1 NYEZZYQZRQDLEH-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 230000007062 hydrolysis Effects 0.000 description 10
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 239000003999 initiator Substances 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 229920002271 DEAE-Sepharose Polymers 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 150000001768 cations Chemical class 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000004255 ion exchange chromatography Methods 0.000 description 7
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 7
- 229960004768 irinotecan Drugs 0.000 description 7
- 125000005936 piperidyl group Chemical group 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- 229920002684 Sepharose Polymers 0.000 description 6
- 125000005677 ethinylene group Chemical class [*:2]C#C[*:1] 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 125000003107 substituted aryl group Chemical group 0.000 description 6
- MNUUNDKDTPELEI-UHFFFAOYSA-N 2-pent-4-ynyl-4,5-dihydro-1,3-oxazole Chemical compound C#CCCCC1=NCCO1 MNUUNDKDTPELEI-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000007334 copolymerization reaction Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 125000005439 maleimidyl group Chemical class C1(C=CC(N1*)=O)=O 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 150000001241 acetals Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 125000005981 pentynyl group Chemical group 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 150000003852 triazoles Chemical class 0.000 description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- GUXJXWKCUUWCLX-UHFFFAOYSA-N 2-methyl-2-oxazoline Chemical group CC1=NCCO1 GUXJXWKCUUWCLX-UHFFFAOYSA-N 0.000 description 2
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000003973 alkyl amines Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 2
- 150000004982 aromatic amines Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- PYMCWVIXPLQKHO-UHFFFAOYSA-N azido hexanoate Chemical compound CCCCCC(=O)ON=[N+]=[N-] PYMCWVIXPLQKHO-UHFFFAOYSA-N 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000005266 diarylamine group Chemical group 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- DZIYAIZKJOHVQC-KLXURFKVSA-N ethyl (2s)-2,6-diaminohexanoate;dihydrochloride Chemical compound Cl.Cl.CCOC(=O)[C@@H](N)CCCCN DZIYAIZKJOHVQC-KLXURFKVSA-N 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 150000003949 imides Chemical class 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
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- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/0233—Polyamines derived from (poly)oxazolines, (poly)oxazines or having pendant acyl groups
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
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- 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
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- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/028—Polyamidoamines
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Immunology (AREA)
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- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
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| US61/029,337 | 2008-02-16 | ||
| PCT/US2009/030762 WO2009089542A2 (en) | 2008-01-11 | 2009-01-12 | Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same |
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|---|---|---|---|---|
| US8101706B2 (en) | 2008-01-11 | 2012-01-24 | Serina Therapeutics, Inc. | Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same |
| CN101959934B (zh) * | 2008-01-11 | 2012-12-12 | 塞瑞纳治疗公司 | 聚噁唑啉共聚物的多官能形式和包含它的药物组合物 |
| WO2010006282A2 (en) * | 2008-07-10 | 2010-01-14 | Serina Therapeutics, Inc. | Polyoxazolines with inert terminating groups, polyoxazolines prepared from protected initiating groups and related compounds |
| TR201909167T4 (tr) | 2011-01-04 | 2019-07-22 | Gatt Tech B V | Elektrofilik olarak aktive edilmiş polioksazolinden derive edilen çapraz bağlı polimerler ve implantlar. |
| CN102731791B (zh) * | 2011-04-13 | 2016-04-13 | 北京大学 | 温度敏感型嵌段共聚物及其水凝胶和其用途 |
| US8383093B1 (en) | 2011-11-01 | 2013-02-26 | Serina Therapeutics, Inc. | Subcutaneous delivery of poly(oxazoline) conjugates |
| US20140271527A1 (en) * | 2011-11-01 | 2014-09-18 | Serina Therapeutics, Inc. | Subcutaneous delivery of polymer conjugates of therapeutic agents |
| BR112014016338B1 (pt) | 2012-01-02 | 2021-01-26 | Universiteit Gent | polímeros de polioxazolina e processos para a sua preparação, conjugados destes polímeros e usos médicos dos mesmos |
| CN104271638B (zh) | 2012-03-16 | 2016-11-02 | 本德尔分析控股公司 | 源于亲核活性聚噁唑啉的交联聚合物和医用品 |
| CA2891673C (en) | 2012-11-15 | 2025-10-07 | Apellis Pharmaceuticals Inc | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
| CN106715533B (zh) * | 2014-07-31 | 2020-03-13 | 塞瑞纳治疗公司 | 聚恶唑啉抗体药物结合物 |
| MY179853A (en) | 2014-09-26 | 2020-11-18 | Alcon Inc | Polymerizable polysiloxanes with hydrophilic substituents |
| BR112017006943B1 (pt) | 2014-10-06 | 2020-12-01 | Gatt Technologies B.V | produto hemostático poroso adesivo de tecido |
| JP6968787B2 (ja) | 2015-10-07 | 2021-11-17 | アペリス・ファーマシューティカルズ・インコーポレイテッドApellis Pharmaceuticals, Inc. | 投与レジメン |
| CN105418911A (zh) * | 2015-12-29 | 2016-03-23 | 南京工业大学 | 一种聚(2-r-2-噁唑啉)嵌段聚(肌氨酸)双亲性嵌段共聚物的制备方法 |
| US11040107B2 (en) | 2017-04-07 | 2021-06-22 | Apellis Pharmaceuticals, Inc. | Dosing regimens and related compositions and methods |
| DE102018000650A1 (de) * | 2018-01-27 | 2019-08-01 | Friedrich-Schiller-Universität Jena | Verfahren zur Bestimmung von Verunreinigungen in Polyalkylenethern oder Polyalkylenaminen und dessen Verwendung |
| US12485181B2 (en) | 2019-06-28 | 2025-12-02 | Serina Therapeutics (Al), Inc. | Polyoxazoline-drug conjugates with novel pharmacokinetic properties |
| CN113354811B (zh) * | 2020-02-19 | 2024-05-07 | 华东理工大学 | 一种侧链含有氨基和/或羟基的噁唑啉聚合物，其制备方法及应用 |
| CN112661961B (zh) * | 2020-12-28 | 2022-05-06 | 中国科学院长春应用化学研究所 | 两亲性聚噁唑啉共聚物、其制备方法及应用 |
| US12233132B2 (en) | 2021-02-09 | 2025-02-25 | Serina Therapeutics, Inc. | Polyoxazoline-lipid conjugates and lipid nanoparticles and pharmaceutical compositions including same |
| AU2022336664A1 (en) | 2021-09-03 | 2024-01-18 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids comprising phosphatidylserine |
| AU2022336209B2 (en) | 2021-09-03 | 2025-10-16 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids |
| KR20230044782A (ko) | 2021-09-27 | 2023-04-04 | 삼성전자주식회사 | 패치 안테나를 포함하는 안테나 구조 및 이를 포함하는 전자 장치 |
| US20250027108A1 (en) | 2021-10-29 | 2025-01-23 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
| US20250099614A1 (en) | 2022-01-28 | 2025-03-27 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
| AU2024233180A1 (en) | 2023-03-08 | 2025-09-25 | CureVac SE | Novel lipid nanoparticle formulations for delivery of nucleic acids |
| WO2024230934A1 (en) | 2023-05-11 | 2024-11-14 | CureVac SE | Therapeutic nucleic acid for the treatment of ophthalmic diseases |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4709039A (en) | 1986-03-21 | 1987-11-24 | The Dow Chemical Company | Vinyloxazoline monomer and preparation thereof |
| JP2003268391A (ja) | 2002-03-13 | 2003-09-25 | Infineum Internatl Ltd | 粒状物トラップを備えるディーゼルエンジン用燃料添加剤組成物 |
| JP2005082810A (ja) | 2003-09-05 | 2005-03-31 | Infineum Internatl Ltd | 安定化ディーゼル燃料添加剤組成物 |
| US20060051315A1 (en) | 2002-02-01 | 2006-03-09 | Scaria Puthupparampil V | Polymers for delivering peptides and small molecules in vivo |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990002144A1 (en) | 1988-08-22 | 1990-03-08 | Fused Kontacts Of Chicago, Inc. | Compositions for making improved gas permeable contact lenses |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| US5130126A (en) | 1990-07-09 | 1992-07-14 | Nippon Oil & Fats Co., Ltd. | Polymer-drug conjugate and a method of producing it |
| US5416071A (en) | 1991-03-12 | 1995-05-16 | Takeda Chemical Industries, Ltd. | Water-soluble composition for sustained-release containing epo and hyaluronic acid |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5635571A (en) | 1995-06-30 | 1997-06-03 | Cornell Research Foundation, Inc. | Polymerizable macromonomers and polymers prepared therefrom |
| US6753165B1 (en) | 1999-01-14 | 2004-06-22 | Bolder Biotechnology, Inc. | Methods for making proteins containing free cysteine residues |
| EP1012184B1 (en) | 1997-07-14 | 2007-10-10 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
| JO2291B1 (en) | 1999-07-02 | 2005-09-12 | اف . هوفمان لاروش ايه جي | Erythropoietin derivatives |
| CZ299516B6 (cs) | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem |
| DE19936014C2 (de) | 1999-08-04 | 2003-04-03 | Zf Lemfoerder Metallwaren Ag | Gummilager mit axialer Dämpfung |
| AU2001289307A1 (en) | 2000-04-06 | 2001-10-23 | Pharmacia Corporation | Chemically-modified myelopoietin conjugates |
| CN1458846A (zh) | 2000-09-08 | 2003-11-26 | 格莱风治疗公司 | 促红细胞生成性合成蛋白 |
| ATE421535T1 (de) | 2000-10-16 | 2009-02-15 | Chugai Pharmaceutical Co Ltd | Peg-modifiziertes erythropoietin |
| US6759496B2 (en) * | 2000-12-18 | 2004-07-06 | Bausch & Lomb Incorporated | Poly(2-oxazoline) biomedical devices |
| AU2002233230B2 (en) | 2000-12-20 | 2007-02-01 | F. Hoffmann-La Roche Ag | Erythropoietin conjugates |
| KR100401296B1 (ko) | 2000-12-27 | 2003-10-11 | 드림바이오젠 주식회사 | 수식물질에 의해 수식된 단백질 변이체 및 이것의 제조방법 |
| US7077939B1 (en) | 2001-06-18 | 2006-07-18 | The Texas A&M University System | Method and apparatus for nanoparticle transport and detection |
| US6908963B2 (en) | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| US7125843B2 (en) | 2001-10-19 | 2006-10-24 | Neose Technologies, Inc. | Glycoconjugates including more than one peptide |
| JP3984541B2 (ja) * | 2001-12-26 | 2007-10-03 | 財団法人川村理化学研究所 | 星型ポリオキサゾリンからなる粒子およびその製造方法 |
| US7074755B2 (en) | 2003-05-17 | 2006-07-11 | Centocor, Inc. | Erythropoietin conjugate compounds with extended half-lives |
| BRPI0410863A (pt) | 2003-05-30 | 2006-07-04 | Centocor Inc | formação de novos conjugados de eritropoietina usando transglutaminase |
| US8057821B2 (en) * | 2004-11-03 | 2011-11-15 | Egen, Inc. | Biodegradable cross-linked cationic multi-block copolymers for gene delivery and methods of making thereof |
| GB2438982A (en) | 2004-12-22 | 2007-12-12 | Ambrx Inc | Compostions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| WO2007010552A2 (en) | 2005-03-17 | 2007-01-25 | Serum Institute Of India Limited | N- terminal peg conjugate of erythropoietin |
| CN106046370A (zh) | 2007-02-28 | 2016-10-26 | 塞瑞纳治疗公司 | 聚噁唑啉poz化合物、合成其的方法、以及靶分子‑poz偶联物 |
| CN101959934B (zh) | 2008-01-11 | 2012-12-12 | 塞瑞纳治疗公司 | 聚噁唑啉共聚物的多官能形式和包含它的药物组合物 |
| US8101706B2 (en) * | 2008-01-11 | 2012-01-24 | Serina Therapeutics, Inc. | Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same |
-
2009
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- 2009-01-12 KR KR1020107017208A patent/KR101486449B1/ko active Active
- 2009-01-12 WO PCT/US2009/030762 patent/WO2009089542A2/en not_active Ceased
- 2009-01-12 DK DK16154587.6T patent/DK3042922T3/en active
- 2009-01-12 JP JP2010542410A patent/JP5514736B2/ja active Active
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- 2009-01-12 EP EP16154587.6A patent/EP3042922B1/en active Active
- 2009-01-12 US US12/744,472 patent/US8110651B2/en active Active
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2012
- 2012-02-06 US US13/367,128 patent/US9169354B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4709039A (en) | 1986-03-21 | 1987-11-24 | The Dow Chemical Company | Vinyloxazoline monomer and preparation thereof |
| US20060051315A1 (en) | 2002-02-01 | 2006-03-09 | Scaria Puthupparampil V | Polymers for delivering peptides and small molecules in vivo |
| JP2003268391A (ja) | 2002-03-13 | 2003-09-25 | Infineum Internatl Ltd | 粒状物トラップを備えるディーゼルエンジン用燃料添加剤組成物 |
| JP2005082810A (ja) | 2003-09-05 | 2005-03-31 | Infineum Internatl Ltd | 安定化ディーゼル燃料添加剤組成物 |
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| WO2009089542A3 (en) | 2009-10-01 |
| EP2235090A4 (en) | 2011-10-05 |
| EP2235090B1 (en) | 2013-09-04 |
| EP3042922A1 (en) | 2016-07-13 |
| DK3042922T3 (en) | 2017-10-23 |
| US20110009594A1 (en) | 2011-01-13 |
| CN101959934A (zh) | 2011-01-26 |
| WO2009089542A2 (en) | 2009-07-16 |
| EP2669313B1 (en) | 2016-03-23 |
| EP2669313A1 (en) | 2013-12-04 |
| KR20110007084A (ko) | 2011-01-21 |
| EP2235090A2 (en) | 2010-10-06 |
| US8110651B2 (en) | 2012-02-07 |
| JP2011510120A (ja) | 2011-03-31 |
| US9169354B2 (en) | 2015-10-27 |
| EP3042922B1 (en) | 2017-07-19 |
| US20120136123A1 (en) | 2012-05-31 |
| CN101959934B (zh) | 2012-12-12 |
| JP5514736B2 (ja) | 2014-06-04 |
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