EP0247860A2
Expired / Lapsed
EP
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Tumor necrosis factor formulation and its preparation
Assignee: Cetus Oncology Corp Te Emeryville Californ
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Filing: 1987-05-27
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Granted: —
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Expires: 2007-05-27
Abstract
Abstract A pharmaceutical composition is prepared utilizing biologically active, selectively conjugated TNF. The conjugation is of TNF to a water-soluble polymer selected from polyethylene glycol polymers or polyoxyethylated polyols, which polyethylene glycol polymer is unsubstituted or substituted at one end with an alkyl group and which polyol is unsubstituted.
Inventors
- 👤 Nandini Katre
- 👤 James William Thomson
- 👤 Michael James Knauf
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 06:31
CPC Classifications
A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/19; A61K38/191; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; A61P; A61P35/00
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
68 words
A pharmaceutical composition comprising a non-toxic, inert, pharmaceutically acceptable aqueous carrier medium in which is dissolved a biologically active selectively conjugated tumor necrosis factor (TNF) wherein the TNF is covalently conjugated to a water-soluble polymer selected from the group consisting of polyethylene glycol polymers and polyoxyethylated polyols, wherein said polyethylene glycol polymer is unsubstituted or substituted at one end with an alkyl group and said polyol is unsubstituted.
Claim 2
Dependent Claim
68 words
A pharmaceutical composition comprising a non-toxic, inert, pharmaceutically acceptable aqueous carrier medium in which is dissolved a biologically active selectively conjugated tumor necrosis factor (TNF) wherein the TNF is covalently conjugated to a water-soluble polymer selected from the group consisting of polyethylene glycol polymers and polyoxyethylated polyols, wherein said polyethylene glycol polymer is unsubstituted or substituted at one end with an alkyl group and said polyol is unsubstituted.
Claim 3
Dependent Claim
22 words
A composition according to claim 1 wherein said polymer is a homopolymer and has a molecular weight of about 3OO to 1OO,OOO.
Claim 4
Dependent Claim
32 words
A composition according to claim 1 or 2 wherein said polymer is conjugated to the TNF via the 4-hydroxy-3-nitrobenzene sulfonate ester or the N-hydroxysuccinimide ester of a carboxylic acid of said polymer.
Claim 5
Dependent Claim
40 words
A composition according to any one of claims 1-3 wherein said polymer is either a homopolymer selected from unsubstituted polyethylene glycol or monomethyl polyethylene glycol, or a polyoxyethylated glycerol, and said TNF is human recombinant TNF or a mutein thereof.
Claim 6
Dependent Claim
96 words
A process for preparing a pharmaceutical composition comprising: (a) preparing a water-soluble polymer having at least one terminal reactive group where said polymer is selected from the group consisting of polyethylene glycol polymers and polyoxyethylated polyols, wherein said polyethylene glycol polymer is unsubstituted or substituted at one end with an alkyl group, and said polyol is unsubstituted; (b) reacting biologically active tumor necrosis factor (TNF) with the reactive group of said polymer so as to provide a biologically active, selectively conjugated TNF; and (c) formulating said TNF in a non-toxic, inert, pharmaceutically acceptable aqueous carrier medium.
Claim 7
Dependent Claim
96 words
A process for preparing a pharmaceutical composition comprising: (a) preparing a water-soluble polymer having at least one terminal reactive group where said polymer is selected from the group consisting of polyethylene glycol polymers and polyoxyethylated polyols, wherein said polyethylene glycol polymer is unsubstituted or substituted at one end with an alkyl group, and said polyol is unsubstituted; (b) reacting biologically active tumor necrosis factor (TNF) with the reactive group of said polymer so as to provide a biologically active, selectively conjugated TNF; and (c) formulating said TNF in a non-toxic, inert, pharmaceutically acceptable aqueous carrier medium.
Claim 8
Dependent Claim
26 words
A process according to claim 5 wherein said polymer has a molecular weight of about 3OO to 1OO,OOO and said TNF is formulated at pH 6-8.
Claim 9
Dependent Claim
48 words
A process according to claim 5 or 6 wherein step (a) comprises reacting the polymer with an acid anhydride to form a carboxylic acid, and reacting the carboxylic acid with a compound capable of reacting with the acid to form said activated polymer with a reactive ester group.
Claim 10
Dependent Claim
34 words
A process according to claim 7 wherein the acid anhydride is glutaric anhydride and the compound capable of reacting with the acid in the presence of a carbodiimide is N-hydroxysuccinimide or 4-hydroxy-3-nitrobenzene sulfonic acid.
Claim 11
Dependent Claim
30 words
A process according to claim 8 wherein the reactive group reacts with one lysine residue of said TNF and step (b) is carried out at a pH of about 8-1O.
Claim 12
Dependent Claim
41 words
1O. A process according to any one of claims 5-9 wherein said TNF is human recombinant TNF or a mutein thereof and said polymer is either a homopolymer selected from unsubstituted polyethylene glycol or monomethyl polyethylene glycol, or a polyoxyethylated glycerol.
References Cited (Backward Citations)
No citation records indexed.
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