CA2515612A1 - Activated polyethylene glycol esters - Google Patents
Activated polyethylene glycol esters Download PDFInfo
- Publication number
- CA2515612A1 CA2515612A1 CA002515612A CA2515612A CA2515612A1 CA 2515612 A1 CA2515612 A1 CA 2515612A1 CA 002515612 A CA002515612 A CA 002515612A CA 2515612 A CA2515612 A CA 2515612A CA 2515612 A1 CA2515612 A1 CA 2515612A1
- Authority
- CA
- Canada
- Prior art keywords
- peg
- protein
- linker
- nucleophile
- conjugate
- 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.)
- Abandoned
Links
- 239000002202 Polyethylene glycol Substances 0.000 title claims abstract description 78
- 229920001223 polyethylene glycol Polymers 0.000 title claims abstract description 78
- 150000002334 glycols Chemical class 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 85
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 85
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 47
- 150000002148 esters Chemical class 0.000 claims abstract description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 25
- 239000012038 nucleophile Substances 0.000 claims description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
- OMAHFYGHUQSIEF-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) oxalate Chemical compound O=C1CCC(=O)N1OC(=O)C(=O)ON1C(=O)CCC1=O OMAHFYGHUQSIEF-UHFFFAOYSA-N 0.000 claims description 14
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 12
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
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- 238000002360 preparation method Methods 0.000 abstract description 12
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 abstract description 10
- 230000006320 pegylation Effects 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 abstract description 2
- MNTLSHJBDKQYOF-UHFFFAOYSA-N 2-oxo-2-[[6-(trifluoromethyl)-2H-benzotriazol-4-yl]oxy]acetic acid Chemical compound C1=C(C=C(C2=NNN=C21)OC(=O)C(=O)O)C(F)(F)F MNTLSHJBDKQYOF-UHFFFAOYSA-N 0.000 abstract 1
- 150000003901 oxalic acid esters Chemical class 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
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- 150000001875 compounds Chemical class 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
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- 125000003277 amino group Chemical group 0.000 description 10
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
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- -1 oxalate ester Chemical class 0.000 description 6
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- 239000000047 product Substances 0.000 description 5
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- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 4
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- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 2
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- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Polyethers (AREA)
- Polyesters Or Polycarbonates (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44835403P | 2003-02-19 | 2003-02-19 | |
| US60/448,354 | 2003-02-19 | ||
| PCT/IB2004/000424 WO2004074345A2 (en) | 2003-02-19 | 2004-02-13 | Carbonate esters of polyethylene glycol activated by means of oxalate esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2515612A1 true CA2515612A1 (en) | 2004-09-02 |
Family
ID=32908577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002515612A Abandoned CA2515612A1 (en) | 2003-02-19 | 2004-02-13 | Activated polyethylene glycol esters |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7094872B2 (enExample) |
| EP (1) | EP1597299A2 (enExample) |
| JP (1) | JP2006517995A (enExample) |
| AR (1) | AR043216A1 (enExample) |
| BR (1) | BRPI0407511A (enExample) |
| CA (1) | CA2515612A1 (enExample) |
| MX (1) | MXPA05008785A (enExample) |
| TW (1) | TW200426155A (enExample) |
| WO (1) | WO2004074345A2 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100729977B1 (ko) | 1999-12-22 | 2007-06-20 | 넥타르 테라퓨틱스 에이엘, 코포레이션 | 폴리(에틸렌 글리콜)의 1-벤조트리아졸릴 카르보네이트에스테르의 제조 방법 |
| DE60315949T2 (de) | 2002-01-16 | 2008-06-12 | Biocompatibles Uk Ltd., Farnham | Polymerkonjugate |
| GB0301014D0 (en) * | 2003-01-16 | 2003-02-19 | Biocompatibles Ltd | Conjugation reactions |
| ITPD20040159A1 (it) * | 2004-06-21 | 2004-09-21 | Univ Degli Studi Trieste | Derivati bifunzionali del polietilenglicole loro preparazione e uso. |
| US8133707B2 (en) * | 2006-01-17 | 2012-03-13 | Enzon Pharmaceuticals, Inc. | Methods of preparing activated polymers having alpha nitrogen groups |
| JP2007209543A (ja) * | 2006-02-09 | 2007-08-23 | Hidetoshi Tsuchida | 表面修飾アルブミンからなる固相膜および酸素吸着膜 |
| WO2007117685A2 (en) | 2006-04-07 | 2007-10-18 | Nektar Therapeutics Al, Corporation | Conjugates of an anti-tnf-alpha antibody |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4342832A (en) * | 1979-07-05 | 1982-08-03 | Genentech, Inc. | Method of constructing a replicable cloning vehicle having quasi-synthetic genes |
| US5618697A (en) * | 1982-12-10 | 1997-04-08 | Novo Nordisk A/S | Process for preparing a desired protein |
| US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| CA2102808A1 (en) * | 1991-05-10 | 1992-11-11 | Hanne Bentz | Targeted delivery of bone growth factors |
| US5281698A (en) * | 1991-07-23 | 1994-01-25 | Cetus Oncology Corporation | Preparation of an activated polymer ester for protein conjugation |
| US5382657A (en) * | 1992-08-26 | 1995-01-17 | Hoffmann-La Roche Inc. | Peg-interferon conjugates |
| US5650234A (en) * | 1994-09-09 | 1997-07-22 | Surface Engineering Technologies, Division Of Innerdyne, Inc. | Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces |
| US5932462A (en) * | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US6180095B1 (en) * | 1997-12-17 | 2001-01-30 | Enzon, Inc. | Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents |
| GB0013810D0 (en) * | 2000-06-06 | 2000-07-26 | Celltech Chiroscience Ltd | Biological products |
-
2004
- 2004-02-13 JP JP2006502450A patent/JP2006517995A/ja not_active Withdrawn
- 2004-02-13 CA CA002515612A patent/CA2515612A1/en not_active Abandoned
- 2004-02-13 BR BRPI0407511-0A patent/BRPI0407511A/pt not_active IP Right Cessation
- 2004-02-13 EP EP04710945A patent/EP1597299A2/en not_active Withdrawn
- 2004-02-13 MX MXPA05008785A patent/MXPA05008785A/es not_active Application Discontinuation
- 2004-02-13 WO PCT/IB2004/000424 patent/WO2004074345A2/en not_active Ceased
- 2004-02-18 AR ARP040100501A patent/AR043216A1/es unknown
- 2004-02-18 TW TW093103934A patent/TW200426155A/zh unknown
- 2004-02-19 US US10/782,268 patent/US7094872B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004074345A2 (en) | 2004-09-02 |
| BRPI0407511A (pt) | 2006-02-14 |
| US7094872B2 (en) | 2006-08-22 |
| JP2006517995A (ja) | 2006-08-03 |
| AR043216A1 (es) | 2005-07-20 |
| EP1597299A2 (en) | 2005-11-23 |
| TW200426155A (en) | 2004-12-01 |
| MXPA05008785A (es) | 2005-10-18 |
| US20040162388A1 (en) | 2004-08-19 |
| WO2004074345A3 (en) | 2005-01-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |