US5281698A
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US
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Preparation of an activated polymer ester for protein conjugation
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1991-07-23
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Granted: 1994-01-25
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Expires: 2011-07-23
Abstract
Abstract The present invention is a process for preparing an activated ester of polyethylene glycol or a polyoxyethylated polyol. After the activated ester is prepared, it can be reacted with a protein to form a polymer/protein conjugate. Conjugation with a polymer can reduce the protein's immunogenicity, increase its solubility, and increase its circulating in vivo half-life. Preferred proteins are IL-2, CSFs, and interferons.
Inventors
- 👤 Danute E. Nitecki
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 12:24
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/30; C07D207/34; C07D207/36; C07D207/40; C07D207/404; C07K; C07K1/00; C07K1/107; C07K1/1072; C07K1/1077; C07K14/00; C07K14/435; C07K14/52; C07K14/53; C07K14/54; C07K14/55; C07K14/555
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
48 words
A method for producing an activated ester of polyethylene glycol (PEG) or a polyoxyethylated polyol, comprising: a) contacting PEG or a polyoxyethylated polyol, which has at least one hydroxyl group, with disuccinimidylcarbonate (DSC) under the appropriate reaction conditions to form a PEG or a polyoxyethylated polyol active ester.
Claim 2
Independent Claim
48 words
A method for producing an activated ester of polyethylene glycol (PEG) or a polyoxyethylated polyol, comprising: a) contacting PEG or a polyoxyethylated polyol, which has at least one hydroxyl group, with disuccinimidylcarbonate (DSC) under the appropriate reaction conditions to form a PEG or a polyoxyethylated polyol active ester.
Claim 3
Dependent Claim
14 words
A method in accordance with claim 1, wherein PEG is activated with the DSC.
Claim 4
Dependent Claim
19 words
A method in accordance with claim 2, wherein the molar ratio of DSC to PEG is 30:1 or less.
Claim 5
Dependent Claim
19 words
A method in accordance with claim 2, wherein the molar ratio of DSC to PEG is 20:1 or less.
Claim 6
Dependent Claim
22 words
A method in accordance with claim 2 further comprising adding a catalyst selected from the group consisting essentially of pyridine or 4-dimethylaminopyridine.
Claim 7
Dependent Claim
23 words
A method in accordance with claim 1, wherein the PEG or the polyoxyethylated polyol has a average molecular weight between 1,000 and 40,000.
Claim 8
Dependent Claim
23 words
A method in accordance with claim 1, wherein the PEG or the polyoxyethylated polyol has a average molecular weight between 2,000 and 20,000.
Claim 9
Independent Claim
23 words
A method in accordance with claim. 1, wherein the PEG or the polyoxyethylated polyol has an average molecular weight between 3,000 and 12,000.
Claim 10
Dependent Claim
12 words
A method in accordance with claim 6, wherein the polymer is PEG.
Claim 11
Dependent Claim
37 words
A method in accordance with claim 1 further comprising: a) contacting the PEG or the polyoxyethylated polyol active ester with a protein under the appropriate reaction conditions to form a PEG or a polyoxyethylated polyol protein conjugate.
Claim 12
Dependent Claim
37 words
A method in accordance with claim 10, wherein the PEG or the polyoxyethylated polyol active ester is contacted with the protein in the molar ratio of between 1 and 30 moles active esters to 1 mole protein.
Claim 13
Dependent Claim
32 words
A method in accordance with claim 11, wherein the active ester is contacted with the protein in the molar ratio of between 1 and 15 moles active esters to 1 mole protein.
Claim 14
Dependent Claim
23 words
A method in accordance with claim 10, wherein the PEG or the polyoxyethylated polyol has a average molecular weight between 1,000 and 40,000.
Claim 15
Dependent Claim
23 words
A method in accordance with claim 10, wherein the PEG or the polyoxyethylated polyol has a average molecular weight between 2,000 and 20,000.
Claim 16
Dependent Claim
23 words
A method in accordance with claim 10, wherein the PEG or the polyoxyethylated polyol has an average molecular weight between 3,000 and 12,000.
Claim 17
Dependent Claim
16 words
A method in accordance with claim 11, wherein the active ester is a PEG active ester.
Claim 18
Dependent Claim
12 words
A method in accordance with claim 11, wherein the protein is IL-2.
Claim 19
Dependent Claim
12 words
A method in accordance with claim 11, wherein the protein is CSF.
Claim 20
Dependent Claim
12 words
A method in accordance with claim 11, wherein the protein is interferon.
Claim 21
Dependent Claim
30 words
A method in accordance with claim 17, wherein the PEG active ester is contacted with IL-2 in the molar ratio around 5 moles of PEG esters to 1 mole IL-2.
References Cited (Backward Citations)
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| 3.5 Years (Year 4) | 1997-01-24 | 1997-07-26 | 1998-01-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-01-24 | 2001-07-26 | 2002-01-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-01-24 | 2005-07-26 | 2006-01-25 | $7700.00 | Window Closed / Lapsed |