Patent US4535771A successfully refreshed from Google Patents.
Patent US4902502A successfully refreshed from Google Patents.
US4902502A
Expired / Lapsed
US
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Preparation of a polymer/interleukin-2 conjugate
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1989-01-23
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Granted: 1990-02-20
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Expires: 2009-01-23
Abstract
Abstract The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.
Inventors
- 👤 Danute E. Nitecki
- 👤 Nandini Katre
- 👤 Robert J. Goodson
- 👤 Lois Aldwin
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:06
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
74 words
A method for producing a PEG/IL-2 conjugate or a polyoxyethylated polyol/IL-2 conjugate, comprising: a. contacting a PEG or a polyoxyethylated polyol, which has at least one hydroxyl group, with a chloroformate under the appropriate reaction conditions to form a PEG or a polyoxyethylated polyol active ester; and b. contacting the PEG or the polyoxyethylated polyol active ester with IL-2 under the appropriate reaction conditions to form a PEG/IL-2 conjugate or a polyoxyethylated polyol/IL-2 conjugate.
Claim 2
Independent Claim
74 words
A method for producing a PEG/IL-2 conjugate or a polyoxyethylated polyol/IL-2 conjugate, comprising: a. contacting a PEG or a polyoxyethylated polyol, which has at least one hydroxyl group, with a chloroformate under the appropriate reaction conditions to form a PEG or a polyoxyethylated polyol active ester; and b. contacting the PEG or the polyoxyethylated polyol active ester with IL-2 under the appropriate reaction conditions to form a PEG/IL-2 conjugate or a polyoxyethylated polyol/IL-2 conjugate.
Claim 3
Dependent Claim
36 words
A method in accordance with claim 1, wherein the PEG or the polyoxyethylated polyol active ester is contacted with the IL-2 in the molar ratio of 1 to 20 moles active esters to one mole IL-2.
Claim 4
Dependent Claim
31 words
A method in accordance with claim 1, wherein the active ester is contacted with the IL-2 in the molar ratio of 6 to 16 moles active esters to one mole IL-2.
Claim 5
Dependent Claim
31 words
A method in accordance with claim 1, wherein the active ester is contacted with the IL-2 in the molar ratio of 10 to 14 moles active esters to one mole IL-2.
Claim 6
Dependent Claim
26 words
A method in accordance with claim 1 wherein the conjugate has a molar ratio of from 1 to 3 PEGs or polyoxyethylated polyols per one IL-2.
Claim 7
Dependent Claim
25 words
A method in accordance with claim 1, wherein the conjugate has a molar ratio of from 2 to 3 PEGs or polyoxyethylated per one IL-2.
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 1000 and 40,000.
Claim 9
Dependent Claim
23 words
A method in accordance with claim 1, wherein the PEG or the polyoxyethylated polyol has a average molecular weight between 2000 and 20,000.
Claim 10
Dependent Claim
23 words
A method in accordance with claim 1, wherein the PEG or the polyoxyethylated polyol has an averaage molecular weight between 3,000 and 12,000.
Claim 11
Dependent Claim
12 words
A method in accordance with claim 4 wherein the polymer is PEG.
Claim 12
Dependent Claim
12 words
A method in accordance with claim 4 wherein the polymer is POG.
Claim 13
Dependent Claim
13 words
A method in accordance with claim 1, wherein the IL-2 is a mutein.
Claim 14
Dependent Claim
28 words
A method in accordance with claim 12, wherein the IL-2 mutein which has up to six N-terminal deletions and the cysteine at position 125 is replaced by serine.
Claim 15
Dependent Claim
16 words
A method in accordance with claim 1, wherein the chloroformate is para-nitrophenyl chloroformate or, ortho-nitrophenyl chloroformate.
Claim 16
Dependent Claim
23 words
A method in accordance with claim 1, wherein the PEG or polyoxyethylated polyol is covalently conjugated to the IL-2 via a urethane bond.
Claim 17
Independent Claim
51 words
A method for producing a PEG/IL-2 conjugate, comprising: a. contacting PEG, which has at least one hydroxyl group, with a chloroformate under the appropriate reaction conditions to form a PEG active ester; and b. contacting the PEG active ester with IL-2 under the appropriate reaction conditions to form a PEG/IL-2 conjugate.
Claim 18
Independent Claim
51 words
A method for producing a PEG/IL-2 conjugate, comprising: a. contacting PEG, which has at least one hydroxyl group, with a chloroformate under the appropriate reaction conditions to form a PEG active ester; and b. contacting the PEG active ester with IL-2 under the appropriate reaction conditions to form a PEG/IL-2 conjugate.
Claim 19
Dependent Claim
32 words
A method in accordance with claim 16, wherein the PEG active ester is contacted with the IL-2 in the molar ratio of 10 to 14 moles PEG esters to one mole IL-2.
Claim 20
Dependent Claim
22 words
A method in accordance with claim 16, wherein the conjugate has a molar ratio of between 1 and 3 PEGs per IL-2.
Claim 21
Dependent Claim
19 words
A method in accordance with claim 16, wherein the PEG has a average molecular weight between 2000 and 20,000.
Claim 22
Dependent Claim
18 words
A method in accordance with claim 16, wherein the PEG has a molecular weight between 3,000 to 12,000.
Claim 23
Dependent Claim
13 words
A method in accordance with claim 16, wherein the IL-2 is a mutein.
Claim 24
Dependent Claim
27 words
A method in accordance with claim 21, wherein IL-2 mutein which has up to six N-terminal deletions and the cysteine at position 125 is replaced by serine.
Claim 25
Dependent Claim
16 words
A method in accordance with claim 16, wherein the chloroformate is para-nitrophenyl chloroformate or, ortho-nitrophenyl chloroformate.
Claim 26
Dependent Claim
20 words
A method in accordance with claim 16, wherein the PEG is covalently conjugated to the IL-2 via a urethane bond.
Claim 27
Independent Claim
46 words
A method for producing a PEG/IL-2 conjugate, comprising contacting PEG, having a terminal hydroxy group, with para-nitrophenyl chloroformate under the appropriate reaction conditions to form a PEG active ester; and contacting the PEG active ester with des-ala ser 125 , IL-2 to form a PEG/IL-2 conjugate.
Claim 28
Independent Claim
46 words
A method for producing a PEG/IL-2 conjugate, comprising contacting PEG, having a terminal hydroxy group, with para-nitrophenyl chloroformate under the appropriate reaction conditions to form a PEG active ester; and contacting the PEG active ester with des-ala ser 125 , IL-2 to form a PEG/IL-2 conjugate.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1993-02-19 | 1993-08-21 | 1994-02-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-02-19 | 1997-08-21 | 1998-02-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-02-19 | 2001-08-21 | 2002-02-20 | $7700.00 | Window Closed / Lapsed |