ES2244006T3 - Bioconjugados y administracion de agentes bioactivos. - Google Patents
Bioconjugados y administracion de agentes bioactivos.Info
- Publication number
- ES2244006T3 ES2244006T3 ES97939382T ES97939382T ES2244006T3 ES 2244006 T3 ES2244006 T3 ES 2244006T3 ES 97939382 T ES97939382 T ES 97939382T ES 97939382 T ES97939382 T ES 97939382T ES 2244006 T3 ES2244006 T3 ES 2244006T3
- Authority
- ES
- Spain
- Prior art keywords
- bioconjugate
- cobalamin
- cells
- bioactive agent
- complex
- 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
- 239000012867 bioactive agent Substances 0.000 title claims abstract description 69
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical group [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims abstract description 36
- 210000000056 organ Anatomy 0.000 claims abstract description 17
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 55
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- -1 cobalamin lactam Chemical class 0.000 claims description 29
- 125000004429 atom Chemical group 0.000 claims description 23
- 239000003550 marker Substances 0.000 claims description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 23
- 239000003446 ligand Substances 0.000 claims description 21
- 108091034117 Oligonucleotide Proteins 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 17
- 108090000623 proteins and genes Proteins 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 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 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 229910017052 cobalt Inorganic materials 0.000 claims description 13
- 239000010941 cobalt Substances 0.000 claims description 13
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 13
- 102000004169 proteins and genes Human genes 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 239000011724 folic acid Substances 0.000 claims description 10
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- 150000007523 nucleic acids Chemical class 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 235000019152 folic acid Nutrition 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 150000001867 cobalamins Chemical class 0.000 claims description 8
- 102000004877 Insulin Human genes 0.000 claims description 7
- 108090001061 Insulin Proteins 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 229940125396 insulin Drugs 0.000 claims description 7
- 229940088594 vitamin Drugs 0.000 claims description 7
- 229930003231 vitamin Natural products 0.000 claims description 7
- 235000013343 vitamin Nutrition 0.000 claims description 7
- 239000011782 vitamin Substances 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000003346 cobalamin group Chemical group 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 108010088751 Albumins Proteins 0.000 claims description 5
- 102000009027 Albumins Human genes 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 5
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 5
- 150000001336 alkenes Chemical class 0.000 claims description 5
- 229960000304 folic acid Drugs 0.000 claims description 5
- 229930182830 galactose Natural products 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 108091033319 polynucleotide Proteins 0.000 claims description 5
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- 102000040430 polynucleotide Human genes 0.000 claims description 5
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 4
- 102000004338 Transferrin Human genes 0.000 claims description 4
- 108090000901 Transferrin Proteins 0.000 claims description 4
- 150000001345 alkine derivatives Chemical class 0.000 claims description 4
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
- 239000005515 coenzyme Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 230000010837 receptor-mediated endocytosis Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000012581 transferrin Substances 0.000 claims description 4
- 108020004491 Antisense DNA Proteins 0.000 claims description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003816 antisense DNA Substances 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 229910052798 chalcogen Inorganic materials 0.000 claims description 3
- 150000001787 chalcogens Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 229940080818 propionamide Drugs 0.000 claims description 3
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- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000003931 anilides Chemical class 0.000 claims description 2
- 229960002685 biotin Drugs 0.000 claims description 2
- 235000020958 biotin Nutrition 0.000 claims description 2
- 239000011616 biotin Substances 0.000 claims description 2
- 150000002763 monocarboxylic acids Chemical class 0.000 claims description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000008707 rearrangement Effects 0.000 claims description 2
- 229910052711 selenium Inorganic materials 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 108020005544 Antisense RNA Proteins 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 239000003184 complementary RNA Substances 0.000 claims 1
- 150000002596 lactones Chemical class 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 239000011669 selenium Substances 0.000 claims 1
- 239000010703 silicon Substances 0.000 claims 1
- 238000006303 photolysis reaction Methods 0.000 abstract description 74
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- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 55
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- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 21
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- VZHHNBNSMNNUAD-UHFFFAOYSA-N cobalt 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound [Co].OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VZHHNBNSMNNUAD-UHFFFAOYSA-N 0.000 description 17
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- 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 12
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
-
- 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
- A61K47/54—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 compound
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2503696P | 1996-08-27 | 1996-08-27 | |
| US2443096P | 1996-08-27 | 1996-08-27 | |
| US24430P | 1996-08-27 | ||
| US25036P | 1996-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2244006T3 true ES2244006T3 (es) | 2005-12-01 |
Family
ID=26698439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97939382T Expired - Lifetime ES2244006T3 (es) | 1996-08-27 | 1997-08-22 | Bioconjugados y administracion de agentes bioactivos. |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US6315978B1 (enExample) |
| EP (1) | EP1007533B1 (enExample) |
| JP (1) | JP2001501596A (enExample) |
| AT (1) | ATE298344T1 (enExample) |
| AU (1) | AU738431B2 (enExample) |
| CA (1) | CA2264592C (enExample) |
| DE (1) | DE69733618T2 (enExample) |
| ES (1) | ES2244006T3 (enExample) |
| NZ (1) | NZ334870A (enExample) |
| PT (1) | PT1007533E (enExample) |
| WO (1) | WO1998008859A1 (enExample) |
Families Citing this family (71)
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| US5739313A (en) * | 1995-11-13 | 1998-04-14 | Regents Of The University Of Minnesota | Radionuclide labeling of vitamin B12 and coenzymes thereof |
| EP1171162A2 (en) * | 1999-04-16 | 2002-01-16 | Mayo Foundation For Medical Education And Research | Cobalamin conjugates useful as antitumor agents |
| US6806363B1 (en) * | 1999-04-16 | 2004-10-19 | Mayo Foundation For Medical Education & Research | Cobalamin conjugates useful as antitumor agents |
| US7591995B2 (en) * | 1999-10-15 | 2009-09-22 | Mayo Foundation For Medical Education And Research | Cobalamin conjugates useful as imaging and therapeutic agents |
| WO2001028592A1 (en) * | 1999-10-15 | 2001-04-26 | Mayo Foundation For Medical Education And Research | Cobalamin conjugates useful as imaging agents and as antitumor agents |
| EP1239887A1 (en) * | 1999-10-15 | 2002-09-18 | Mayo Foundation For Medical Education And Research | Cobalamin conjugates useful as imaging and therapeutic agents |
| US7067111B1 (en) | 1999-10-25 | 2006-06-27 | Board Of Regents, University Of Texas System | Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging |
| US6797521B2 (en) | 1999-10-26 | 2004-09-28 | University Of Utah Research Foundation | Fluorescent cobalamins and uses thereof |
| DE10012120A1 (de) * | 2000-03-13 | 2001-09-27 | Ktb Tumorforschungs Gmbh | Therapeutische und diagnostische Ligandensysteme mit Transportmolekülbindenden Eigenschaften und diese enthaltende Arzneimittel |
| US20020042394A1 (en) * | 2000-05-31 | 2002-04-11 | Hogenkamp Henricus P.C. | Cobalamin compounds useful as antibiotic agents and as imaging agents |
| US20020049155A1 (en) * | 2000-05-31 | 2002-04-25 | Hogenkamp Henricus P.C. | Cobalamin compounds useful as cardiovascular agents and as imaging agents |
| CA2410906C (en) | 2000-06-02 | 2012-10-02 | Board Of Regents, The University Of Texas System | Ethylenedicysteine (ec)-drug conjugates |
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| CA2427146A1 (en) * | 2000-10-25 | 2002-07-18 | Mayo Foundation For Medical Education And Research | Transcobalamin binding conjugates useful for treating abnormal cellular proliferation |
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| WO2002076394A2 (en) * | 2001-03-22 | 2002-10-03 | The Ohio State University Research Foundation | Enzyme-based anti-cancer compositions and methods |
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| US20030031627A1 (en) * | 2001-07-31 | 2003-02-13 | Mallinckrodt Inc. | Internal image antibodies for optical imaging and therapy |
| WO2003026674A1 (en) * | 2001-09-28 | 2003-04-03 | Mayo Foundation For Medical Education And Research | Coadministration of transport protein with conjugated cobalamin to deliver agents |
| US6679827B2 (en) | 2001-10-11 | 2004-01-20 | Robert E. Sandstrom | Magnetic field enhancement of tumor treatment |
| US9657294B2 (en) | 2002-02-20 | 2017-05-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| US20040047917A1 (en) * | 2002-09-06 | 2004-03-11 | Stephen Wilson | Drug delivery and targeting with vitamin B12 conjugates |
| US7627373B2 (en) | 2002-11-30 | 2009-12-01 | Cardiac Pacemakers, Inc. | Method and apparatus for cell and electrical therapy of living tissue |
| EP1596815A4 (en) * | 2003-02-20 | 2007-07-04 | Cleveland Clinic Foundation | COMPOSITION AND METHOD FOR INHIBITING THE SURVIVAL OF CELLS |
| US7232805B2 (en) * | 2003-09-10 | 2007-06-19 | Inflabloc Pharmaceuticals, Inc. | Cobalamin conjugates for anti-tumor therapy |
| US7119065B2 (en) * | 2003-10-29 | 2006-10-10 | Nagoya Industrial Science Research Institute | Metal complex-protein composite and oxidation catalyst |
| US9050378B2 (en) | 2003-12-10 | 2015-06-09 | Board Of Regents, The University Of Texas System | N2S2 chelate-targeting ligand conjugates |
| US7840263B2 (en) * | 2004-02-27 | 2010-11-23 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression |
| US7764995B2 (en) | 2004-06-07 | 2010-07-27 | Cardiac Pacemakers, Inc. | Method and apparatus to modulate cellular regeneration post myocardial infarct |
| US7729761B2 (en) * | 2004-07-14 | 2010-06-01 | Cardiac Pacemakers, Inc. | Method and apparatus for controlled gene or protein delivery |
| EP1789391B1 (en) | 2004-07-23 | 2017-06-28 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| US8202507B2 (en) * | 2004-09-23 | 2012-06-19 | The Regents Of The University Of California | Assay for vitamin B12 absorption and method of making labeled vitamin B12 |
| US7981065B2 (en) | 2004-12-20 | 2011-07-19 | Cardiac Pacemakers, Inc. | Lead electrode incorporating extracellular matrix |
| US8060219B2 (en) | 2004-12-20 | 2011-11-15 | Cardiac Pacemakers, Inc. | Epicardial patch including isolated extracellular matrix with pacing electrodes |
| EP1893038A1 (en) * | 2005-05-17 | 2008-03-05 | Cargill, Incorporated | Granular lecithins, granular lysolecithins, process for their production and compositions containing them |
| WO2007022494A2 (en) * | 2005-08-19 | 2007-02-22 | Endocyte, Inc. | Multi-drug ligand conjugates |
| US7774057B2 (en) | 2005-09-06 | 2010-08-10 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression for cardiac protection |
| PT1965787E (pt) * | 2005-11-30 | 2013-07-05 | Endo Pharmaceuticals Inc | Tratamento de xerostomia com um antioxidante que contém enxofre |
| US10925977B2 (en) | 2006-10-05 | 2021-02-23 | Ceil>Point, LLC | Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications |
| US20100104626A1 (en) | 2007-02-16 | 2010-04-29 | Endocyte, Inc. | Methods and compositions for treating and diagnosing kidney disease |
| US8883723B2 (en) | 2007-03-05 | 2014-11-11 | Syracuse University | Conjugate of insulin and vitamin B12 for oral delivery |
| CN104127878A (zh) | 2007-03-14 | 2014-11-05 | 恩多塞特公司 | 结合配体连接的微管溶素递药缀合物 |
| AU2008229041A1 (en) * | 2007-03-19 | 2008-09-25 | Inflabloc Pharmaceuticals, Inc. | Cobalamin taxane bioconjugates |
| CA2687291A1 (en) | 2007-05-16 | 2008-11-20 | Ktb Tumorforschungsgesellschaft Mbh | Low-viscous anthracycline formulation |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| WO2009002993A1 (en) | 2007-06-25 | 2008-12-31 | Endocyte, Inc. | Conjugates containing hydrophilic spacer linkers |
| US8684898B2 (en) * | 2007-10-18 | 2014-04-01 | The Invention Science Fund I Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| US20090104113A1 (en) * | 2007-10-18 | 2009-04-23 | Searete Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| US8529426B2 (en) * | 2007-10-18 | 2013-09-10 | The Invention Science Fund I Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| US8227204B2 (en) * | 2007-10-18 | 2012-07-24 | The Invention Science Fund I, Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| GB2453860B (en) | 2007-10-18 | 2011-03-16 | Searete Llc | Ionizing-radiation-responsive compositions,methods and systems |
| US8164074B2 (en) * | 2007-10-18 | 2012-04-24 | The Invention Science Fund I, Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| US9557635B2 (en) | 2007-10-18 | 2017-01-31 | Gearbox, Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| US8168958B2 (en) * | 2007-10-18 | 2012-05-01 | The Invention Science Fund I, Llc | Ionizing-radiation-responsive compositions, methods, and systems |
| US20090169484A1 (en) | 2007-12-28 | 2009-07-02 | Ihi Corporation | Iron-salen complex |
| JP2009274962A (ja) * | 2008-05-12 | 2009-11-26 | Yoshihiro Ishikawa | 鉄サレン錯体、磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 |
| US20100016256A1 (en) * | 2008-07-21 | 2010-01-21 | Gebhard John R | Taxane Compounds for Treating Eye Disease |
| EP2357166B1 (en) | 2008-11-20 | 2020-01-15 | IHI Corporation | Auto magnetic metal salen complex compound |
| CN102834512A (zh) * | 2010-04-06 | 2012-12-19 | 株式会社Ihi | 金属salen配合物衍生物及其制造方法 |
| WO2011130716A2 (en) | 2010-04-16 | 2011-10-20 | Access Pharmaceuticals, Inc. | A nanostructures containing vitamin b12 for facilitated delivery of drugs across biological barriers |
| US20120231069A1 (en) | 2011-03-08 | 2012-09-13 | Access Pharmaceuticals, Inc. | Targeted Nanocarrier Systems for Delivery of Actives Across Biological Membranes |
| US10080805B2 (en) | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| KR20150070318A (ko) | 2012-10-16 | 2015-06-24 | 엔도사이트, 인코포레이티드 | 비천연 아미노산을 함유하는 약물 전달 컨쥬게이트 및 사용 방법 |
| EP2968599A4 (en) * | 2013-03-14 | 2016-11-09 | Albany Molecular Res Inc | LIGAND THERAPEUTIC ACID JUGATES AND LINKERS ON SILICON BASE |
| WO2014168950A1 (en) * | 2013-04-08 | 2014-10-16 | University Of North Carolina At Chapel Hill | Photo-responsive compounds |
| KR102295648B1 (ko) * | 2013-05-22 | 2021-08-31 | 알닐람 파마슈티칼스 인코포레이티드 | ＳＥＲＰＩＮＡ1 ｉＲＮＡ 조성물 및 이의 사용 방법 |
| CN105658230B (zh) * | 2013-08-29 | 2020-04-21 | 希望之城 | 细胞穿透缀合物及其使用方法 |
| GR20130100654A (el) * | 2013-11-22 | 2015-06-18 | Χρηστος Γκολφινου Ταπεινος | Επιφανειακως τροποποιημενα πολλαπλως αποκρινομενα σε ερεθισματα νανο/μικρο-δοχεια ως φορεις φαρμακων για στοχευμενη θεραπεια διαφορων μορφων καρκινου |
| WO2020113130A1 (en) * | 2018-11-29 | 2020-06-04 | The Trustees Of Dartmouth College | Tumor targeting vitamin b12 derivatives for x-ray activated chemotherapy |
| GB202018713D0 (en) | 2020-11-27 | 2021-01-13 | Quadram Inst Bioscience | Methods and compositions utilising vitamin b12 binding |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4758421A (en) * | 1985-03-15 | 1988-07-19 | The Board Of Trustees Of The Leland Stanford Junior University | Bleomycin conjugates and method |
| NZ217821A (en) * | 1985-10-10 | 1989-07-27 | Biotech Australia Pty Ltd | Oral delivery system; complex of active agent and vitamin b12 or analogue thereof |
| JP3095752B2 (ja) * | 1987-07-15 | 2000-10-10 | アメリカ合衆国 | Ｔａｇ‐７２及びヒト癌腫に対して結合特異性を有する第二世代モノクローナル抗体及びその使用方法 |
| US5047227A (en) * | 1988-02-08 | 1991-09-10 | Cytogen Corporation | Novel and improved antibodies for site specific attachment of compounds |
| IL93982A0 (en) * | 1989-04-03 | 1991-01-31 | Purdue Research Foundation | Method for enhancing transmembrane transport of exogenous molecules |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5763569A (en) * | 1991-08-23 | 1998-06-09 | The Brigham And Women's Hospital, Inc | Calcium receptor-active molecules |
| EP0698040A4 (en) * | 1993-05-20 | 1999-01-07 | Biotech Australia Pty Ltd | LHRH ANTAGONISTS |
| US5548064A (en) * | 1993-05-24 | 1996-08-20 | Biotech Australia Pty Limited | Vitamin B12 conjugates with EPO, analogues thereof and pharmaceutical compositions |
| JPH10502334A (ja) * | 1994-04-08 | 1998-03-03 | レセプタゲン・コーポレーション | 受容体調節剤およびこれに関連した方法 |
| US5574018A (en) * | 1994-07-29 | 1996-11-12 | Amgen Inc. | Conjugates of vitamin B12 and proteins |
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1997
- 1997-08-22 PT PT97939382T patent/PT1007533E/pt unknown
- 1997-08-22 US US09/202,328 patent/US6315978B1/en not_active Expired - Fee Related
- 1997-08-22 AU AU41482/97A patent/AU738431B2/en not_active Ceased
- 1997-08-22 NZ NZ334870A patent/NZ334870A/xx not_active IP Right Cessation
- 1997-08-22 DE DE69733618T patent/DE69733618T2/de not_active Expired - Lifetime
- 1997-08-22 JP JP10511674A patent/JP2001501596A/ja active Pending
- 1997-08-22 EP EP97939382A patent/EP1007533B1/en not_active Expired - Lifetime
- 1997-08-22 ES ES97939382T patent/ES2244006T3/es not_active Expired - Lifetime
- 1997-08-22 WO PCT/US1997/014140 patent/WO1998008859A1/en not_active Ceased
- 1997-08-22 AT AT97939382T patent/ATE298344T1/de active
- 1997-08-22 CA CA2264592A patent/CA2264592C/en not_active Expired - Fee Related
-
2001
- 2001-10-22 US US09/982,940 patent/US6790827B2/en not_active Expired - Lifetime
- 2001-10-22 US US09/982,892 patent/US6776976B2/en not_active Expired - Lifetime
- 2001-10-22 US US09/982,968 patent/US6777237B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998008859A1 (en) | 1998-03-05 |
| DE69733618D1 (de) | 2005-07-28 |
| EP1007533A4 (en) | 2002-08-07 |
| NZ334870A (en) | 2000-12-22 |
| CA2264592A1 (en) | 1998-03-05 |
| AU4148297A (en) | 1998-03-19 |
| US6777237B2 (en) | 2004-08-17 |
| AU738431B2 (en) | 2001-09-20 |
| CA2264592C (en) | 2012-02-21 |
| PT1007533E (pt) | 2005-09-30 |
| US20020111294A1 (en) | 2002-08-15 |
| ATE298344T1 (de) | 2005-07-15 |
| US20020049154A1 (en) | 2002-04-25 |
| EP1007533A1 (en) | 2000-06-14 |
| DE69733618T2 (de) | 2006-05-11 |
| EP1007533B1 (en) | 2005-06-22 |
| JP2001501596A (ja) | 2001-02-06 |
| US6315978B1 (en) | 2001-11-13 |
| US6776976B2 (en) | 2004-08-17 |
| US6790827B2 (en) | 2004-09-14 |
| US20020115595A1 (en) | 2002-08-22 |
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