CA2336663C - Coumarin and related aromatic-based polymeric prodrugs - Google Patents
Coumarin and related aromatic-based polymeric prodrugs Download PDFInfo
- Publication number
- CA2336663C CA2336663C CA002336663A CA2336663A CA2336663C CA 2336663 C CA2336663 C CA 2336663C CA 002336663 A CA002336663 A CA 002336663A CA 2336663 A CA2336663 A CA 2336663A CA 2336663 C CA2336663 C CA 2336663C
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- compound
- group
- alkyls
- aryls
- 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 - Fee Related
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- 239000000651 prodrug Substances 0.000 title claims abstract description 88
- 229940002612 prodrug Drugs 0.000 title claims abstract description 88
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 33
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title description 20
- 229960000956 coumarin Drugs 0.000 title description 10
- 235000001671 coumarin Nutrition 0.000 title description 10
- 229920000642 polymer Polymers 0.000 claims abstract description 48
- -1 nitro, carboxyl Chemical group 0.000 claims abstract description 36
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 150000001412 amines Chemical class 0.000 claims abstract description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 19
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 15
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 15
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
- 125000002252 acyl group Chemical group 0.000 claims abstract description 13
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 11
- 239000003574 free electron Substances 0.000 claims abstract description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000004405 heteroalkoxy group Chemical group 0.000 claims abstract description 9
- 125000004429 atom Chemical group 0.000 claims abstract description 8
- 230000000890 antigenic effect Effects 0.000 claims abstract description 7
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 7
- 125000006575 electron-withdrawing group Chemical group 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical class 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims abstract 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 16
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 6
- 150000001875 compounds Chemical class 0.000 claims description 125
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- 238000000034 method Methods 0.000 claims description 32
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 14
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- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 3
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- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
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- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
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- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 235000010460 mustard Nutrition 0.000 claims description 3
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
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- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
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- 238000001727 in vivo Methods 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 229960003272 asparaginase Drugs 0.000 description 8
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 229940123237 Taxane Drugs 0.000 description 7
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 7
- 230000021615 conjugation Effects 0.000 description 7
- 238000007273 lactonization reaction Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
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- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
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- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 5
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- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 5
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- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
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- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
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- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- HTYIXCKSEQQCJO-UHFFFAOYSA-N phenaglycodol Chemical compound CC(C)(O)C(C)(O)C1=CC=C(Cl)C=C1 HTYIXCKSEQQCJO-UHFFFAOYSA-N 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
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- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
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- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
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- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 229930191090 pradimicin Natural products 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
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- 229940097325 prolactin Drugs 0.000 description 1
- NSETWVJZUWGCKE-UHFFFAOYSA-N propylphosphonic acid Chemical compound CCCP(O)(O)=O NSETWVJZUWGCKE-UHFFFAOYSA-N 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000009736 ragweed Nutrition 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyrrole Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/114,860 US6214330B1 (en) | 1998-07-13 | 1998-07-13 | Coumarin and related aromatic-based polymeric prodrugs |
| US09/114,860 | 1998-07-13 | ||
| PCT/US1999/015652 WO2000002568A1 (en) | 1998-07-13 | 1999-07-12 | Coumarin and related aromatic-based polymeric prodrugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2336663A1 CA2336663A1 (en) | 2000-01-20 |
| CA2336663C true CA2336663C (en) | 2009-10-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002336663A Expired - Fee Related CA2336663C (en) | 1998-07-13 | 1999-07-12 | Coumarin and related aromatic-based polymeric prodrugs |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6214330B1 (enExample) |
| EP (1) | EP1102592B1 (enExample) |
| JP (1) | JP4999226B2 (enExample) |
| AT (1) | ATE266424T1 (enExample) |
| AU (1) | AU4983999A (enExample) |
| CA (1) | CA2336663C (enExample) |
| DE (1) | DE69917281T2 (enExample) |
| DK (1) | DK1102592T3 (enExample) |
| WO (1) | WO2000002568A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004264958B2 (en) | 2003-08-13 | 2010-04-15 | Biocon, Ltd | Micro-particle fatty acid salt solid dosage formulations for therapeutic agents |
| US7534902B2 (en) * | 2003-11-14 | 2009-05-19 | Wisconsin Alumni Research Foundation | Fluorescence assays with improved sensitivity |
| US20090214472A1 (en) * | 2004-03-01 | 2009-08-27 | Enzon Pharmaceuticals Inc. | Interferon-beta polymer conjugates |
| JP2007533750A (ja) * | 2004-04-21 | 2007-11-22 | アルザ コーポレイション | 緩和なチオール分解条件下で遊離可能なポリマー結合体 |
| MXPA06012144A (es) * | 2004-04-21 | 2007-01-31 | Alza Corp | Conjugado polimerico liberable bajo condiciones tioliticas suaves. |
| US8367065B2 (en) * | 2006-09-15 | 2013-02-05 | Enzon Pharmaceuticals, Inc. | Targeted polymeric prodrugs containing multifunctional linkers |
| JP2010503708A (ja) * | 2006-09-15 | 2010-02-04 | エンゾン ファーマスーティカルズ インコーポレイテッド | 多官能性リンカーを含む標的化ポリマープロドラッグ |
| CA2693645A1 (en) * | 2007-07-11 | 2009-01-15 | Enzon Pharmaceuticals, Inc. | Polymeric drug delivery systems containing an aromatic allylic acid |
| BRPI0818004B8 (pt) | 2007-10-16 | 2021-05-25 | Biocon Ltd | composição farmacêutica sólida administrável por via oral e o processo da mesma. |
| US20100227327A1 (en) * | 2008-08-08 | 2010-09-09 | Xiaoliang Sunney Xie | Methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides |
| US20100036110A1 (en) * | 2008-08-08 | 2010-02-11 | Xiaoliang Sunney Xie | Methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides |
| JP6747971B2 (ja) | 2013-10-15 | 2020-08-26 | シアトル ジェネティックス， インコーポレイテッド | 改善されたリガンド−薬物コンジュゲート薬物動態のためのｐｅｇ化薬物−リンカー |
| US11229708B2 (en) | 2015-12-04 | 2022-01-25 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| EP3433278A4 (en) | 2016-03-25 | 2019-11-06 | Seattle Genetics, Inc. | METHOD FOR THE PRODUCTION OF PEGYLATED ACTIVE LINKERS AND INTERMEDIATE PRODUCTS THEREOF |
| CN110430901B (zh) | 2017-03-24 | 2024-08-16 | 西雅图基因公司 | 制备葡糖苷酸药物-接头及其中间体的方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4399282A (en) * | 1979-07-10 | 1983-08-16 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives |
| US4943579A (en) * | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
| FR2676058B1 (fr) | 1991-04-30 | 1994-02-25 | Hoechst Lab | Prodrogues glycosylees, leur procede de preparation et leur utilisation dans le traitement des cancers. |
| EP0727992A4 (en) * | 1993-10-20 | 2001-01-31 | Enzon Inc | SUBSTITUTED TAXOID SUBSTANCES IN 2 'AND / OR 7' POSITION |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| ES2227536T3 (es) | 1995-06-27 | 2005-04-01 | Pharmachemie B.V. | Nuevos profarmacos de antraciclina, procedimiento de preparacion asi como su uso en quimioterapia selectiva. |
| JPH1087815A (ja) * | 1996-08-22 | 1998-04-07 | Enzon Inc | ポリアルキレンオキシドカルボン酸の改良製造方法 |
| EP0961619A4 (en) | 1996-09-27 | 2001-09-26 | Bristol Myers Squibb Co | HYDROLYSABLE DRUGS FOR THE RELEASE OF ANTI-CANCER DRUGS IN METASTATIC CELLS |
-
1998
- 1998-07-13 US US09/114,860 patent/US6214330B1/en not_active Expired - Lifetime
-
1999
- 1999-07-12 DK DK99933882T patent/DK1102592T3/da active
- 1999-07-12 DE DE69917281T patent/DE69917281T2/de not_active Expired - Lifetime
- 1999-07-12 AT AT99933882T patent/ATE266424T1/de not_active IP Right Cessation
- 1999-07-12 JP JP2000558827A patent/JP4999226B2/ja not_active Expired - Fee Related
- 1999-07-12 CA CA002336663A patent/CA2336663C/en not_active Expired - Fee Related
- 1999-07-12 EP EP99933882A patent/EP1102592B1/en not_active Expired - Lifetime
- 1999-07-12 AU AU49839/99A patent/AU4983999A/en not_active Abandoned
- 1999-07-12 WO PCT/US1999/015652 patent/WO2000002568A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002520288A (ja) | 2002-07-09 |
| AU4983999A (en) | 2000-02-01 |
| EP1102592A1 (en) | 2001-05-30 |
| WO2000002568A1 (en) | 2000-01-20 |
| CA2336663A1 (en) | 2000-01-20 |
| US6214330B1 (en) | 2001-04-10 |
| ATE266424T1 (de) | 2004-05-15 |
| DE69917281D1 (de) | 2004-06-17 |
| DE69917281T2 (de) | 2005-06-30 |
| DK1102592T3 (da) | 2004-08-16 |
| JP4999226B2 (ja) | 2012-08-15 |
| EP1102592A4 (en) | 2001-12-19 |
| EP1102592B1 (en) | 2004-05-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |