US4766106A
Expired / Lapsed
US
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Solubilization of proteins for pharmaceutical compositions using polymer conjugation
Assignee: Cetus Oncology Corp
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Filing: 1988-01-25
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Granted: 1988-08-23
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Expires: 2008-01-25
Abstract
Abstract A pharmaceutical composition is prepared wherein a biologically active conjugated protein which is β-interferon, interleukin-2, or an immunotoxin is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated protein, which is not water-soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to a water-soluble polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols.
Inventors
- 👤 Nandini Katre
- 👤 Michael J. Knauf
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 08:03
CPC Classifications
C; C07; C07K; C07K1/00; C07K1/107; C07K1/1072; C07K1/1077; A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/19; A61K38/20; A61K38/2013; A61K38/21; A61K38/215; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61K47/6819; A61K47/6825; A61K47/6827
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
90 words
A pharmaceutical preparation comprising a non-toxic, inert, pharmaceutically acceptable aqueous carrier medium in which is dissolved an immunotherapeutic effective amount of biologically active, selectively conjugated, recombinant interleukin-2 protein, wherein the protein is covalently conjugated via up to ten amino acid residues on the protein to a water-soluble polymer selected from the group consisting of polyethylene glycol homopolymers and polyoxyethylated polyols, wherein said homopolymer is unsubstituted or substituted at one end with an alkyl group and said polyol is unsubstituted and wherein said protein in its unconjugated form is normally hydrophobic.
Claim 2
Dependent Claim
90 words
A pharmaceutical preparation comprising a non-toxic, inert, pharmaceutically acceptable aqueous carrier medium in which is dissolved an immunotherapeutic effective amount of biologically active, selectively conjugated, recombinant interleukin-2 protein, wherein the protein is covalently conjugated via up to ten amino acid residues on the protein to a water-soluble polymer selected from the group consisting of polyethylene glycol homopolymers and polyoxyethylated polyols, wherein said homopolymer is unsubstituted or substituted at one end with an alkyl group and said polyol is unsubstituted and wherein said protein in its unconjugated form is normally hydrophobic.
Claim 3
Dependent Claim
17 words
The preparation of claim 1 wherein said polymer has a molecular weight of about 300 to 100,000.
Claim 4
Dependent Claim
16 words
The preparation of claim 1 wherein said polymer has a molecular weight of 350 to 40,000.
Claim 5
Dependent Claim
29 words
The preparation of claim 1 wherein said polymer is conjugated to the protein via the 4-hydroxy-3-nitrobenzene sulfonate ester or the N-hydroxysuccinimide ester of a carboxylic acid of said polymer.
Claim 6
Dependent Claim
23 words
The preparation of claim 4 wherein said polymer is an unsubstituted polyethylene glycol homopolymer, a monomethyl polyethylene glycol homopolymer or a polyoxyethylated glycerol.
Claim 7
Dependent Claim
19 words
The preparation of claim 1 wherein the medium is at a pH of about 5-8 and contains a buffer.
Claim 8
Dependent Claim
19 words
The preparation of claim 1 wherein the medium is at a pH of about 6.5-7.8 and contains a buffer.
Claim 9
Dependent Claim
13 words
The preparation of claim 1 wherein the protein is from a human source.
Claim 10
Dependent Claim
20 words
The preparation of claim 1 wherein said protein is selectively conjugated via one or two lysine residues on the protein.
Claim 11
Dependent Claim
20 words
The preparation of claim 1 wherein said protein is selectively conjugated via three to ten lysine residues on the protein.
Claim 12
Dependent Claim
12 words
The preparation of claim 8 wherein the protein is an interleukin-2 mutein.
Claim 13
Dependent Claim
29 words
The preparation of claim 11 wherein said mutein has the amino acid(s) which are at position(s) 104 and/or 125 in the native protein substituted with a neutral amino acid.
Claim 14
Dependent Claim
33 words
The preparation of claim 12 wherein said mutein is ser 125 IL-2, des-ala 1 IL-2, des-ala 1 ser 125 IL-2, des-ala 1 ala 104 IL-2, or des-ala 1 ala 104 ser 125 IL-2.
Claim 15
Dependent Claim
20 words
The preparation of claim 1 wherein said protein is selectively conjugated via up to ten lysine residues on the protein.
Claim 16
Dependent Claim
59 words
A composition comprising biologically active, normally hydrophobic recombinant interleukin-2 protein that is covalently conjugated via up to ten amino acid residues on the protein to a water-soluble polymer selected from the group consisting of polyethylene glycol homopolymers and polyoxyethylated polyols, wherein said homopolymer is unsubstituted or substituted at one end with an alkyl group and said polyol is unsubstituted.
Claim 17
Dependent Claim
59 words
A composition comprising biologically active, normally hydrophobic recombinant interleukin-2 protein that is covalently conjugated via up to ten amino acid residues on the protein to a water-soluble polymer selected from the group consisting of polyethylene glycol homopolymers and polyoxyethylated polyols, wherein said homopolymer is unsubstituted or substituted at one end with an alkyl group and said polyol is unsubstituted.
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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) | 1991-08-23 | 1992-02-22 | 1992-08-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-08-23 | 1996-02-22 | 1996-08-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-08-23 | 2000-02-22 | 2000-08-23 | $7700.00 | Window Closed / Lapsed |