Patent ID: 8058385
Filing Date: 2011-11-15
Classification: A61K,C07D,C08G

Abstract:
1. A method for preparing a conjugate, comprising combining, under conjugation conditions, a thiol-containing biologically active agent with a plurality of maleimide-terminated, water-soluble polymers, the plurality of maleimide-terminated, water-soluble polymers having been prepared by: a) combining a composition comprising a plurality of amine-terminated, water-soluble polymers, each amine-terminated, water-soluble polymer in the plurality encompassed by the structure, wherein POLY is a water-soluble polymer, (c) is zero or one, and X with a composition comprising a plurality of maleimide reagents, each maleimide reagent in the plurality encompassed by the structure, wherein Y Y (a) is an integer from 1 to 20, R R R R under substantially nonaqueous conditions to form a composition comprising a plurality of substituted maleamic acid-terminated, water-soluble polymers, each substituted maleamic acid-terminated, water-soluble polymer in the plurality encompassed by the structure, wherein POLY is a water-soluble polymer, (b) is zero or one, X Y Y (a) is an integer from 1 to 20, R R R R b) isolating the substituted maleamic acid-terminated, water-soluble polymer to form a composition wherein at least about 90% of all polymer species in the composition are substituted maleamic acid-terminated, water-soluble polymers; c) forming a dissolved substituted maleamic acid-terminated, water-soluble polymer composition by dissolving substituted maleamic acid-terminated, water-soluble polymers contained within the substituted maleamic acid-terminated, water-soluble polymer composition; and d) exposing the dissolved substituted maleamic acid-terminated, water-soluble polymer composition to elimination conditions to thereby result in a composition comprising a plurality of maleimide-terminated, water-soluble polymers, each maleimide-terminated, water-soluble polymer in the plurality encompassed by the structure, wherein, POLY is a water-soluble polymer, (b) is zero or one, X R R wherein the elimination conditions comprise conditions selected from the group consisting of heating, addition of a drying agent, and combinations thereof.