Patent US4726783A successfully refreshed from Google Patents.
US5089261A
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Preparation of a polymer/interleukin-2 conjugate
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1989-09-29
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Granted: 1992-02-18
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Expires: 2009-09-29
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 its 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 00:26
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
76 words
A pharmaceutically and therapeutically useful protein comprising a PEG or a polyoxyethylated polyol IL-2 conjugate made by 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 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
Dependent Claim
76 words
A pharmaceutically and therapeutically useful protein comprising a PEG or a polyoxyethylated polyol IL-2 conjugate made by 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 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
22 words
A PEG or a polyoxyethylated polyol IL-2 conjugate comprising PEG or a polyoxyethylated polyol covalently conjugated to IL-2 through a urethane bond.
Claim 4
Dependent Claim
22 words
A PEG or a polyoxyethylated polyol IL-2 conjugate comprising PEG or a polyoxyethylated polyol covalently conjugated to IL-2 through a urethane bond.
Claim 5
Dependent Claim
21 words
A PEG or a polyoxyethylated polyol IL-2 conjugate having the structure: ##STR4## wherein R is the PEG or the polyoxyethylated polyol.
Claim 6
Dependent Claim
21 words
A PEG or a polyoxyethylated polyol IL-2 conjugate having the structure: ##STR4## wherein R is the PEG or the polyoxyethylated polyol.
Claim 7
Dependent Claim
23 words
A conjugate in accordance with claim 2, wherein the conjugate has a molar ratio of from 1 and 3 PEGs per one IL-2.
Claim 8
Dependent Claim
23 words
A conjugate in accordance with claim 2, wherein the conjugate has a molar ratio of from 2 and 3 PEGs per one IL-2.
Claim 9
Dependent Claim
13 words
A conjugate in accordance with claim 2, wherein the IL-2 is a mutein.
Claim 10
Dependent Claim
27 words
A conjugate in accordance with claim 6, wherein the IL-2 mutein has up to six N-terminal deletions, and the cystein at position 125 is replaced by serine.
Claim 11
Dependent Claim
27 words
A therapeutically useful formulation comprising a PEG/IL-2 conjugate, wherein the PEG is covalently attached to IL-2 via a urethane bond, and at least one pharmaceutically acceptable excipient.
Claim 12
Dependent Claim
27 words
A therapeutically useful formulation comprising a PEG/IL-2 conjugate, wherein the PEG is covalently attached to IL-2 via a urethane bond, and at least one pharmaceutically acceptable excipient.
Claim 13
Dependent Claim
7 words
A PEG/IL-2 conjugate having the structure: ##STR5##
Claim 14
Dependent Claim
7 words
A PEG/IL-2 conjugate having the structure: ##STR5##
Claim 15
Dependent Claim
26 words
A therapeutically useful formulation in accordance with claim 8, wherein the at least one excipient comprises amino acids, polymers, polyols, sugars, buffers, preservatives, or other proteins.
Claim 16
Dependent Claim
71 words
A therapeutically useful formulation in accordance with claim 10, wherein the excipients are selected from the group consisting essentially of octylphenoxy polyethoxy ethanol compounds, polyethylene glycol monostereate compounds, polyoxyethylene sorbitan fatty acid esters, sucrose, fructose, dextrose, maltose, glucose, dextran, mannitol, sorbitol, inositol, galactitol, xylitol, lactose, trehalose, bovine or human serum albumin, citrate, acetate, Ringer's and Hank's solutions, saline, phosphate, cysteine, arginine, carnitine, alanine, glycine, lysine, valine, leucine, polyvinylpyrrilolidone, or polyethylene glycol.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-02-17 | 1995-08-19 | 1996-02-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-02-17 | 1999-08-19 | 2000-02-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-02-17 | 2003-08-19 | 2004-02-18 | $7700.00 | Window Closed / Lapsed |