US5091176A
Expired / Lapsed
US
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Polymer-modified peptide drugs having enhanced biological and pharmacological activities
Assignee: WR Grace and Co Conn
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Filing: 1990-04-24
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Granted: 1992-02-25
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Expires: 2010-04-24
Abstract
Abstract Biocompatible polymers derived from isocyanate-capped high molecular weight triols and higher polyols are covalently linked to drugs. These polymer-modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, increased circulating half-life of the drug due to longer residence time in circulation, ability to administer multiple drugs together, and enhanced potency of the drug.
Inventors
- 👤 James A. Braatz
- 👤 Aaron H. Heifetz
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 01:51
CPC Classifications
C; C08; C08G; C08G18/00; C08G18/06; C08G18/28; C08G18/40; C08G18/48; C08G18/4833; C08G18/4837; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; C08G18/08; C08G18/10; C08G18/2805; C08G18/2815; C08G18/283; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/812; Y10S530/815; Y10S530/816
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
115 words
A method for enhancing biological or pharmacological activity of a biologically active peptide comprising preparing an aqueous solution of a liquid polymer-modified version of said peptide by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Claim 2
Independent Claim
115 words
A method for enhancing biological or pharmacological activity of a biologically active peptide comprising preparing an aqueous solution of a liquid polymer-modified version of said peptide by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Claim 3
Dependent Claim
16 words
The method of claim 1 wherein the polymer-modified peptide is less immunogenic than the peptide alone.
Claim 4
Dependent Claim
18 words
The method of claim 1 wherein the polymer-modified peptide has a longer circulating half-life than the peptide alone.
Claim 5
Dependent Claim
23 words
The method of claim 1 wherein the peptide is selected from the group consisting of alkaline phosphatase, hemoglobin, YIGSR, YRGDS, GRGDSPAC, and GHK.
Claim 6
Dependent Claim
16 words
The method of claim 1 wherein more than one peptide is covalently bound to the prepolymer.
Claim 7
Dependent Claim
16 words
The method of claim 1 wherein said polyisocyanate is isophorone diisocyanate or methylene bis (cyclohexyl diisocyanate).
Claim 8
Dependent Claim
128 words
An improved method of producing a biological or pharmacological response in a human being or animal by administration of a biologically active peptide, the improvement comprising administering an aqueous solution of a liquid polymer-modified version of said peptide prepared by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Claim 9
Dependent Claim
128 words
An improved method of producing a biological or pharmacological response in a human being or animal by administration of a biologically active peptide, the improvement comprising administering an aqueous solution of a liquid polymer-modified version of said peptide prepared by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Claim 10
Dependent Claim
9 words
The method of claim 7 which promotes wound healing.
Claim 11
Dependent Claim
11 words
The method of claim 8 wherein said wound is a burn.
Claim 12
Dependent Claim
14 words
The method of claim 8 wherein said peptide contains the sequence RGD or GHK.
Claim 13
Dependent Claim
12 words
The method of claim 7 which inhibits tumor cell growth and metastasis.
Claim 14
Dependent Claim
12 words
The method of claim 11 wherein said peptide contains the sequence RGD.
Claim 15
Dependent Claim
9 words
The method of claim 7 which inhibits atherosclerotic activity.
Claim 16
Dependent Claim
22 words
The method of claim 7 wherein said polymer-modified peptide is admixed with at least one pharmaceutically acceptable carrier prior to being administered.
Claim 17
Dependent Claim
11 words
The method of claim 7 wherein an aqueous solution is administered.
Claim 18
Dependent Claim
16 words
The method of claim 7 wherein more than one peptide is covalently bound to the polymer.
Claim 19
Dependent Claim
16 words
The method of claim 7 wherein the polymer-modified peptide is less immunogenic than the peptide alone.
Claim 20
Dependent Claim
18 words
The method of claim 7 wherein the polymer-modified peptide has a longer circulating half-life than the peptide alone.
Claim 21
Independent Claim
122 words
A method of treating a disease state or condition comprising administration of an aqueous solution of a pharmaceutically active amount of a liquid polymer-modified biologically active peptide, wherein said polymer-modified peptide is prepared by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Claim 22
Independent Claim
122 words
A method of treating a disease state or condition comprising administration of an aqueous solution of a pharmaceutically active amount of a liquid polymer-modified biologically active peptide, wherein said polymer-modified peptide is prepared by covalently binding said peptide to a biocompatible prepolymer under aqueous conditions, wherein said prepolymer is a triol or higher polyol made up of at least 75% oxyethylene monomers, said polyol having a molecular weight of about 7,000 to about 30,000, said polyol having essentially all of the hydroxyl groups capped with aliphatic or cycloaliphatic polyisocyanates, wherein said covalent bond is between an isocyanate group of said prepolymer and an amino, sulfhydryl, carboxyl or hydroxyl group of said peptide, wherein the amount of chain extended insoluble material is reduced.
Claim 23
Dependent Claim
16 words
The method of claim 19 wherein the polymer-modified peptide is less immunogenic than the peptide alone.
Claim 24
Dependent Claim
18 words
The method of claim 17 wherein the polymer-modified peptide has a longer circulating half-life than the peptide alone.
Claim 25
Dependent Claim
9 words
The method of claim 19 which promotes wound healing.
Claim 26
Dependent Claim
11 words
The method of claim 22 wherein said wound is a burn.
Claim 27
Dependent Claim
12 words
The method of claim 19 which inhibits tumor cell growth and metastasis.
Claim 28
Dependent Claim
9 words
The method of claim 19 which inhibits artherosclerotic activity.
Claim 29
Dependent Claim
22 words
The method of claim 19 wherein said polymer-modified peptide is admixed with at least one pharmaceutically acceptable carrier prior to being administered.
Claim 30
Dependent Claim
11 words
The method of claim 19 wherein an aqueous solution is administered.
Claim 31
Dependent Claim
16 words
The method of claim 19 wherein more than one peptide is covalently bound to the polymer.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1995-02-24 | 1995-08-26 | 1996-02-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-02-24 | 1999-08-26 | 2000-02-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-02-24 | 2003-08-26 | 2004-02-25 | $7700.00 | Window Closed / Lapsed |