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US 2022/0088112 A1Published application
Functionalized poly-adp-ribose polymers for drug delivery
AssigneeUniversity of Southern California
InventorYong Zhang
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Abstract
Novel antibody-drug conjugates (ADCs) and methods of using such ADCs to treat proliferative disorders are described herein. The ADCs may comprise a PARP protein automodified with a plurality of poly-ADP-ribose polymers functionalized with novel NAD+ analogues. The automodified PARP with functionalized poly-ADP-ribose polymers provide a novel type of drug carrier, which allows facile conjugation of monoclonal antibodies and cytotoxic drug in high ratios.
Claims20
An antibody-drug conjugate comprising:
- a modified poly ADP-ribose polymerase (PARP) comprising a plurality of poly ADP-ribose (ADPr) groups, the ADPr groups comprising substitutions with one or more alkyne or azido moieties;
- a targeting moiety conjugated to the modified PARP;
- and
- an active agent conjugated to the modified PARP.
1 more element
A method of preparing an antibody-drug conjugate comprising:
- combining a linker and a targeting moiety to provide an antibody-linker conjugate;
- combining a PARP and a substituted dinucleotide to provide an automodified PARP comprising a plurality of poly ADP-ribose (ADPr) groups on a surface of the automodified PARP, wherein the substituted dinucleotide comprises one or more alkyne or azido groups;
- and
- combining the automodified PARP, the antibody-linker conjugate, and an active agent under suitable conditions such that the antibody-linker conjugate and an active agent conjugate to the substituted dinucleotide through click chemistry;
- to provide the antibody drug conjugate.
2 more elements
Dependencies are inferred from the claim text.