HYDROXYL-POLYMER-DRUG-PROTEIN CONJUGATES

摘要

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric scaffold having one or more -LD-D, the PBRM being connected to the polymeric scaffold by Lp, wherein the polymeric scaffold comprises a linear, branched or cyclic polymer having four or more —OH groups. Each occurrence of D is independently a therapeutic agent having a molecular weight <5 kDa. LD and Lp are linkers connecting the therapeutic agent and PBRM to the polymeric scaffold respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

主权项

1. A polymeric scaffold useful to conjugate with a protein based recognition-molecule (PBRM), the scaffold comprising a linear, branched or cyclic polymer having one or more —OH groups connected to the polymer, one or moreconnected to the polymer, and one or moreconnected to the polymer, wherein:
the polymer is a hydroxyl polymer having a molecular weight ranging from 2 kDa to 300 kDa and the polymer is not a polyacetal or a polyketal, each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa; LD1 is a carbonyl-containing moiety; each occurrence ofindependently is a first linker that contains a biodegradable bond so that when the bond is broken, D is released in an active form for its intended therapeutic effect; in which each u independently is an integer 0 or 1, and thebetween LD1 and D denotes direct or indirect attachment of D to LD1; and
each occurrence ofindependently is a second linker not yet connected to PBRM, in which LP2 is a moiety containing a functional group that is capable of forming a covalent bond with a functional group of a PBRM, each u independently is an integer 0 or 1, and thebetween LD1 and LP2 denotes direct or indirect attachment of LP2 to LD1, and each occurrence of the second linker is distinct from each occurrence of the first linker.