Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites

摘要

The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

主权项

1. A method of preparing a modified polyglutamic acid (PGA) molecule comprising:
(a) reacting one or more carboxylic acid groups on the PGA molecule with a carbodiimide and (i) an amine-containing acetylene molecule or (ii) an amine-containing azide molecule to form an acetylene-derivatized or azide-derivatized PGA molecule; (b) reacting other carboxylic acid groups of the acetylene-derivatized or azide-derivatized PGA molecule with a carbodiimide and a maleimido amine to form a maleimide-appended, acetylene- or azide-derivatized PGA molecule; (c) reacting the maleimide-appended, acetylene-derivatized PGA molecule with an acetylene-derivatized drug moiety or the maleimide-appended, azide-derivatized PGA molecule with an acetylene-derivatized drug moiety to form a maleimide-appended, drug modified PGA molecule; and (d) coupling the maleimide-appended, drug modified PGA molecule with a thiol-containing compound comprising a recognition moiety to form a recognition moiety-appended, drug-modified PGA molecule.