Methods for preparing polymeric reagents and compositions of polymeric reagents

Patent metadata

Field	Value
Publication number	US-9732189-B2
Application number	US-201615097105-A
Country	US
Kind code	B2
Filing date	Apr 12, 2016
Priority date	Jul 29, 2005
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

Methods for preparing active carbonate esters of water-soluble polymers are provided. Also provided are other methods related to the active carbonate esters of water-soluble polymers, as well as corresponding compositions.

First claim

What is claimed is:

1. A synthetic method comprising:
(a) combining a composition comprising an aprotic solvent and a hydroxy-terminated, methoxypolyethylene glycol having the following structure:
CH 3 O—(CH 2 CH 2 O) n —CH 2 CH 2 —OH

wherein (n) is an integer from 2 to about 4000, with a composition comprising p-nitrophenyl chloroformate, wherein the composition comprising the p-nitrophenyl chloroformate contains an excess of the p-nitrophenyl chloroformate relative to the hydroxy-terminated, methoxypolyethylene glycol, to thereby result in a composition comprising an active carbonate ester of the methoxypolyethylene glycol having the following structure:

wherein (n) is an integer from 2 to about 4000, and unreacted p-nitrophenyl chloroformate;
(b) adding a composition comprising a reactive molecule selected from the group consisting of water, hydrogen sulfide, and a lower alkyl monobasic amine to the composition from step (a) comprising the active carbonate ester of the methoxypolyethylene glycol and unreacted p-nitrophenyl chloroformate, wherein (i) the composition comprising the reactive molecule is added such that substantially all of the unreacted p-nitrophenyl chloroformate is substantially consumed, and (ii) the compositions resulting from step (a) are not isolated prior to step (b).

Assignees

• Nektar Therapeutics

Inventors

• Kozlowski Antoni
• Mckannan Jon
• Mcmanus Samuel P

Classifications

• A61K47/50

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• C08L71/02

  Polyalkylene oxides · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C08G65/48

  Polymers modified by chemical after-treatment · CPC title

• C08G65/332

  containing carboxyl groups, or halides, or esters thereof · CPC title